Extragonadal germ cell tumors: A clinicopathologic study with emphasis on molecular features, clinical outcomes and associated secondary malignancies.

Extragonadal germ cell tumors (EGCTs) are rare, representing <5% of all germ cell tumors (GCTs). Whilst EGCTs share morphological and immunohistochemical features with their gonadal counterparts, they tend to be more aggressive and are frequently associated with secondary somatic malignancies. The aim of our study was to evaluate the clinical, morphological and immunohistochemical features, and to analyze tumors for chromosomal abnormalities of 12p, in addition to any novel genetic alterations, in a series of EGCTs. Seventy-seven EGCTs were included. Anterior mediastinum was the most common anatomic site, followed by central nervous system, retroperitoneum, sacroccygeal area, and neck. Whole genome SNP array identified isochromosome 12p in 26% of tumors. Additional cytogenetic abnormalities included the presence of gain of chr 21 in 37% of tumors. Somatic-type malignancies were identified in 8% of patients. Disease progression (metastasis and/or recurrence) was documented in 8 patients, most of whom died from their relapse. Three patients who died of disease had somatic-type malignancies. Mediastinal seminomas had a significantly better overall survival when compared to mediastinal non-seminomatous GCTs. Our study demonstrates that EGCTs share similar histologic features, but diverse clinical outcomes compared to their gonadal counterparts. Outcomes vary according to anatomic location and histologic subtypes. Our data corroborate that somatic-type malignancies are frequently encountered in mediastinal EGCTs and that their presence portends a poorer prognosis.

Conventional Cytogenetic Analysis and Array CGH + SNP Identify Essential Thrombocythemia and Prefibrotic Primary Myelofibrosis Patients Who Are at Risk for Disease Progression.

The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (prePMF). In this study, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and array Comparative Genomic Hybridization + Single Nucleotide Polymorphism (aCGH + SNP) in patients with ET or prePMF to determine whether the combined analysis of both methodologies can identify patients who may be at a higher risk of disease progression. We performed a comprehensive genomic review on 169 patients with a clinical diagnosis of ET (154 patients) or prePMF (15 patients). Genomic alterations detected by CC or array-CGH + SNP were detected in 36% of patients. In patients who progressed, 68% had an abnormal genomic finding by either technology. There was a shorter progression-free survival (PFS) among patients who were cytogenetically abnormal or who were cytogenetically normal but had an abnormal aCGH + SNP result. Leveraging the ability to detect submicroscopic copy number alterations and regions of copy neutral-loss of heterozygosity, we identified a higher number of patients harboring genomic abnormalities than previously reported. These results underscore the importance of genomic analysis in prognostication and provide valuable information for clinical management and treatment decisions.

Genetic evaluation for twin pregnancies using karyotyping and single nucleotide polymorphism array analysis.

The study aimed to assess chromosomal abnormalities in twin pregnancies using karyotyping and SNP array analysis. The research involved 530 twin pregnancies from two prenatal diagnosis centers between October 2012 and October 2022. Two types of twin pregnancies were considered: monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA), with a total of 177 MCDA and 353 DCDA cases. Chromosomal abnormalities were examined based on chorionic and amniotic sac properties and clinical indications. Among 42 twin pregnancies, 50 fetuses showed chromosomal abnormalities by karyotyping, with 35 cases of aneuploidy in DCDA and 10 in MCDA. Trisomy 21 was the most common aberration, affecting 15 fetuses in DCDA and 4 in MCDA. The rate of discordant karyotypes in MCDA and DCDA groups was 1.1% and 8.8%, respectively. Ultrasound abnormalities and advanced maternal age were frequent indications (55.3% and 39.2%, respectively). Aneuploidy frequencies in DCDA and MCDA pregnancies with advanced maternal age were 10.6% and 4.5%. Cardiac defects and increased nuchal translucency were common anomalies, with higher incidences of chromosomal abnormalities in DCDA (12.5% and 6.9%) and MCDA groups (23.5% and 3.7%). SNP array identified 1.6% clinically significant copy number variants in DCDA fetuses with ultrasound abnormalities, while no significant CNVs were found in MCDA pregnancies. Chromosomal aneuploidies were the primary abnormalities in twin pregnancies, with detectable abnormalities and clinically significant CNVs more likely in DCDA pregnancies, especially those with ultrasound abnormalities.

Prenatal diagnosis and genetic etiology analysis of talipes equinovarus by chromosomal microarray analysis.

BACKGROUND: With the advancement of molecular technology, fetal talipes equinovarus (TE) is believed to be not only associated with chromosome aneuploidy, but also related to chromosomal microdeletion and microduplication. The study aimed to explore the molecular etiology of fetal TE and provide more information for the clinical screening and genetic counseling of TE by Chromosomal Microarray Analysis (CMA). METHODS: This retrospectively study included 131 fetuses with TE identified by ultrasonography. Conventional karyotyping and SNP array analysis were performed for all the subjects. They were divided into isolated TE group (n = 55) and complex group (n = 76) according to structural anomalies. RESULTS: Among the total of 131 fetuses, karyotype analysis found 12(9.2%) abnormal results, while SNP array found 27 (20.6%) cases. Trisomy 18 was detected most frequently among abnormal karyotypes. The detection rate of SNP array was significantly higher than that of traditional chromosome karyotype analysis (P < 0.05). SNP array detected 15 (11.5%) cases of submicroscopic abnormalities that karyotype analysis did not find. The most common CNV was the 22q11.2 microdeletion. For both analyses, the overall detection rates were significantly higher in the complex TE group than in the isolated TE group (karyotype: P < 0.05; SNP array: P < 0.05). The incremental yield of chromosomal abnormalities in fetuses with unilateral TE (22.0%) was higher than in fetuses with bilateral TE (19.8%), but this difference was not statistically significant (P > 0.05). Abnormal chromosomes were most frequently detected in fetuses with TE plus cardiovascular system abnormalities. CONCLUSION: Fetal TE is related to chromosomal microdeletion or microduplication. Prenatal diagnosis is recommended for fetuses with TE, and CMA testing is preferred. CMA can improve the detection rate of chromosomal abnormalities associated with fetal TE, especially in pregnancies with complex TE.

Single nucleotide polymorphism array (SNP-array) analysis for fetuses with abnormal nasal bone.

PURPOSE: This study aims to evaluate the prevalence of submicroscopic chromosomal abnormalities found on single nucleotide polymorphism array (SNP array) in pregnancies with either an absent or hypoplastic nasal bone. METHODS: This retrospective study included 333 fetuses with either nasal bone hypoplasia or absence identified on prenatal ultrasound. SNP array analysis and conventional karyotyping were performed in all the subjects. The prevalence of chromosomal abnormalities was adjusted for maternal age and other ultrasound findings. Fetuses with either an isolated nasal bone absence or hypoplasia, those that had additional soft ultrasound markers, and those where structural defects were found on ultrasound were divided into three groups: A, B, and C, respectively. RESULTS: Among the total cohort of 333 fetuses, 76 (22.8%) had chromosomal abnormalities, including 47 cases of trisomy 21, 4 cases of trisomy 18, 5 cases of sex chromosome aneuploidy, and 20 cases of copy number variations of which 12 were pathogenic or likely pathogenic. The prevalence of chromosomal abnormalities in group A (n = 164), B (n = 79), and C (n = 90) was 8.5%, 29.1% and 43.3%, respectively. The incremental yields by SNP-array compared with karyotyping in group A, B, and C were 3.0%, 2.5% and 10.7%, respectively (p > 0.05). Compared to karyotype analysis, SNP array detected an additional 2 (1.2%), 1 (1.3%), and 5 (5.6%) pathogenic or likely pathogenic CNVs in groups A, B, and C, respectively. In the 333 fetuses, the prevalence of chromosomal abnormalities in women with advanced maternal age (AMA) was significantly higher than that in non-AMA women, (47.8% vs. 16.5%, p < 0.05). CONCLUSION: In addition to Down's syndrome, many other chromosomal abnormalities are present in fetuses with abnormal nasal bone. SNP array can improve the prevalence of chromosomal abnormalities associated with nasal bone abnormalities, especially in pregnancies with non-isolated nasal bone abnormalities and advanced maternal age.

Prenatal diagnosis of non-mosaic sex chromosome abnormalities: a 10-year experience from a tertiary referral center.

OBJECTIVES: The aim of this study was to explore the frequency and profile of non-mosaic sex chromosome abnormalities detected in prenatal diagnosis over the past 10 years. METHODS: We retrospectively reviewed pregnancies diagnosed with non-mosaic sex chromosome abnormalities between January 2012 and December 2021, using karyotyping and/or single nucleotide polymorphism (SNP) array. Maternal age, indications for testing, and outcomes were recorded. RESULTS: Traditional karyotyping identified 269 (0.90 %) cases of non-mosaic sex chromosome abnormalities among 29,832 fetuses, including 249 cases of numerical abnormalities, 15 unbalanced structural abnormalities, and 5 balanced structural abnormalities. The overall detection rate of common sex chromosome aneuploidies (SCAs) was 0.81 %, with 47,XXY, 47,XXX, 47,XYY, and 45,X accounting for 0.32 , 0.19, 0.17, and 0.13 % respectively. All showed a fluctuating upward trend over the study period, except for 45,X. During the first five years (2012-2016), the major indication for testing was advanced maternal age (AMA), followed by abnormal ultrasound, abnormal noninvasive prenatal testing (NIPT), and abnormal maternal serum screening (MSS). In the second five years (2017-2021), the most frequent indication was abnormal NIPT, followed by AMA, abnormal ultrasound, and abnormal MSS. Among the 7,780 cases that underwent SNP array in parallel, an additional 29 clinically significant aberrations were detected. The most frequent aberration was a microdeletion in the Xp22.31 region, which was associated with X-linked ichthyosis. CONCLUSIONS: Fetal sex chromosome abnormalities are important findings in prenatal diagnosis. The application of NIPT and SNP array technology has greatly improved the detection of SCAs and submicroscopic aberrations associated with sex chromosomes.

Maternally inherited deletion encompassing the RTL1as and MEG8 genes of the human 14q32 imprinted region in a patient with a mild Kagami-Ogata syndrome phenotype.

Kagami-Ogata syndrome and Temple syndrome are imprinting disorders caused by the abnormal expression of genes in an imprinted cluster on chromosome 14q32. Here, we report a female with mild features of the Kagami-Ogata syndrome phenotype with polyhydramnios, neonatal hypotonia, feeding difficulties, abnormal foot morphology, patent foramen ovale, distal arthrogryposis, normal facial profile, and a bell-shaped thorax without coat hanger ribs. The single nucleotide polymorphism array revealed the interstitial deletion of chromosome 14q32.2-q32.31 (117 kb in size), involving the RTL1as and MEG8 genes, and other small nucleolar RNAs and microRNAs. The differentially methylated regions (DMRs) appeared unaltered. The RTL1as gene deletion and the normal methylation pattern of the MEG3 gene loci were confirmed by methylation-specific multiplex ligation-dependent probe amplification. Deletions of the 14q32 region without involving DMRs, and encompassing only the RTL1as and MEG8 genes, are poorly described in the literature. The mother's chromosomal microarray also confirmed the identical 14q32.2 deletion, although she presented a normal phenotype. The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient. It was not sufficient, however, to produce Temple syndrome or any other pathogenic phenotype in the patient's mother.

Fetal genetic findings by chromosomal microarray analysis and karyotyping for fetal growth restriction without structural malformations at a territory referral center: 10-year experience.

BACKGROUND: Prenatal invasive genetic testing is commonly recommended to pregnancies of early-onset FGR or FGR combined with a structural defect. Our study aimed to explore the genetic findings for FGR without structural malformations according to cytogenetic karyotyping and single nucleotide polymorphism array (SNP array) technology over a 10-year period. METHODS: A total of 488 pregnancies diagnosed with FGR without structural malformation were retrospectively reviewed. Cytogenetic karyotyping was performed on all the subjects, and SNP array was available from 272 of them. Based on the gestational age at onset, the cohort was classified into four groups: ≤ 24, 25-28, 29-32, and > 32 weeks of gestation. According to the ultrasound findings, they were grouped into isolated FGR, FGR with soft markers, and FGR with non-structural anomalies. In pregnancies of young maternal age, based on the results of maternal serum screening (MSS), they were categorized into high-risk and low-risk MSS groups. RESULTS: Nineteen (3.9%) cases of chromosomal abnormalities were detected by cytogenetic karyotyping, including 11 cases of numerical abnormalities, 5 cases of structural abnormalities, and 3 cases of mosaicism. Trisomy 21 was the most frequent abnormality. Abnormal karyotypes were more frequently observed in cases diagnosed at ≤ 24 weeks (7.2%) than those in any other group. Among pregnancies with normal karyotype, an incremental yield of 4.2% were revealed by SNP array technology regarding clinically relevant aberrations. The additional detection rates by SNP array in cases diagnosed at ≤ 24 weeks (6.5%), cases with soft markers (9.5%), and cases with high-risk MSS (12.0%) were higher than those in other groups within each classification. All the cases with abnormal karyotypes and 7 out of 11 pregnancies with clinically relevant anomalies revealed by SNP array alone resulted in pregnancy terminations. CONCLUSION: Chromosome abnormality is an important etiology for FGR with no associated structural malformations, and plays a crucial role in pregnancies decision-making. SNP array improves the detection of genetic anomalies especially in FGR diagnosed at ≤ 24 weeks, FGR combined with soft makers, and FGR combined with high-risk MSS.

Prenatal diagnosis of Simpson-Golabi-Behmel syndrome type 1 with an 814 kb Xq26.2 deletion with the initial presentation of a thick nuchal fold.

OBJECTIVE: Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is a rare X-linked recessive disorder characterized by overgrowth and multiple anomalies. Most clinical diagnoses of SGBS1 are made postnatally. We present the case of a pregnant woman in whom the fetus presented with a thick nuchal fold 5.6 mm at 15 weeks of gestation, leading to the prenatal diagnosis of SGBS1 with Xq26.2 (133408101-134221889) deletion. CASE REPORT: We report the case of a 34-year-old pregnant woman with the initial presentation of fetal thick nuchal fold 5.6 mm at 15 weeks of gestation. Amniocentesis of the fetal karyotype revealed a normal 46, XY, and single nucleotide polymorphism array showed Xq26.2 (133408101-134221889) deletion. Prenatal ultrasound at 21 weeks of gestation revealed a thick nuchal fold, hepatomegaly, nephromegaly, congenital diaphragmatic hernia, hypospadias, and polyhydramnios. Fetal magnetic resonance imaging revealed hepatomegaly, nephromegaly, congenital diaphragmatic hernia, and right lung hypoplasia. The woman had her pregnancy terminated at 24 weeks of gestation. The proband had a general appearance of low-set ears, hypertelorism, a large tongue, and hypospadias and some unique findings on autopsy, including hepatomegaly, right hiatal hernia, liver extensive extramedullary hematopoiesis, kidney marked congestion, and focal hemorrhage. DISCUSSION: The main prenatal ultrasound findings that alert clinical doctors about the possible diagnosis of SGBS1 included macrosomia, polyhydramnios, organomegaly, renal malformations, congenital diaphragmatic hernia, and cardiac anomalies. Our case underscores the importance of fetal karyotyping combined with single nucleotide polymorphism array when a thick nuchal fold is found. Genetic counseling is essential in SGBS1, and prenatal testing or preimplantation testing for subsequent pregnancies is necessary to identify possible pathogenic variants.

Rice Pangenome Genotyping Array: an efficient genotyping solution for pangenome-based accelerated genetic improvement in rice.

The advent of the pangenome era has unraveled previously unknown genetic variation existing within diverse crop plants, including rice. This untapped genetic variation is believed to account for a major portion of phenotypic variation existing in crop plants. However, the use of conventional single reference-guided genotyping often fails to capture a large portion of this genetic variation leading to a reference bias. This makes it difficult to identify and utilize novel population/cultivar-specific genes for crop improvement. Thus, we developed a Rice Pangenome Genotyping Array (RPGA) harboring probes assaying 80K single-nucleotide polymorphisms (SNPs) and presence-absence variants spanning the entire 3K rice pangenome. This array provides a simple, user-friendly and cost-effective (60-80 USD per sample) solution for rapid pangenome-based genotyping in rice. The genome-wide association study (GWAS) conducted using RPGA-SNP genotyping data of a rice diversity panel detected a total of 42 loci, including previously known as well as novel genomic loci regulating grain size/weight traits in rice. Eight of these identified trait-associated loci (dispensable loci) could not be detected with conventional single reference genome-based GWAS. A WD repeat-containing PROTEIN 12 gene underlying one of such dispensable locus on chromosome 7 (qLWR7) along with other non-dispensable loci were subsequently detected using high-resolution quantitative trait loci mapping confirming authenticity of RPGA-led GWAS. This demonstrates the potential of RPGA-based genotyping to overcome reference bias. The application of RPGA-based genotyping for population structure analysis, hybridity testing, ultra-high-density genetic map construction and chromosome-level genome assembly, and marker-assisted selection was also demonstrated. A web application (http://www.rpgaweb.com) was further developed to provide an easy to use platform for the imputation of RPGA-based genotyping data using 3K rice reference panel and subsequent GWAS.

Retrospective analysis of the sex chromosomal copy number variations in 186 fetuses using single nucleotide polymorphism arrays.

Sex chromosomal abnormalities are associated with multiple defects. However, the types of sex chromosomal abnormalities during pregnancy in Fujian Province, China, are not recorded. In this retrospective analysis, we showed the sex chromosomal abnormalities of 186 fetuses, including 162 cases of X chromosomal abnormalities and 22 cases of Y chromosomal abnormalities in Fujian Province. We detected 73 cases of Turner syndrome, 24 cases of triple X syndrome, 37 cases of Klinefelter syndrome, and 14 cases of XYY syndrome. It was observed that 67.3% fetuses with classic Turner syndrome had their growth arrested. Moreover, we found 21 cases of mosaic Turner syndrome, 3 cases of mosaic Triple X syndrome, 2 cases of mosaic Klinefelter syndrome, and 1 case of mosaic XYY syndrome. Furthermore, 37 cases of large scales of sex chromosomal deletions/duplications were detected, including 30 cases of X chromosomal deletions/duplications and 7 cases of Y chromosomal deletions/duplications. Parent-of-origins of five cases of sex chromosomal deletions/duplications were determined. One case was with de novo X chromosomal variations, while the sex chromosomal deletions/duplications in other four cases were inherited from their parents. Overall, our results presented a detailed manifestation of sex chromosomal abnormalities of 186 fetuses in Fujian Province and suggested the important roles of single nucleotide polymorphism (SNP) array analysis in the prenatal diagnosis of sex chromosomal abnormalities. Also, determining the parent-of-origins of the deletions/duplications was critical for the prenatal diagnosis of sex chromosomal abnormalities.

Clinical findings and genetic analysis of patients with copy number variants involving 17p13.3 using a single nucleotide polymorphism array: a single-center experience.

BACKGROUND: 17p13.3 microdeletions or microduplications (collectively known as copy number variants or CNVs) have been described in individuals with neurodevelopmental disorders. However, 17p13.3 CNVs were rarely reported in fetuses. This study aims to investigate the clinical significance of 17p13.3 CNVs with varied sizes and gene content in prenatal and postnatal samples. METHODS: Eight cases with 17p13.3 CNVs out of 8806 samples that had been subjected to single nucleotide polymorphism array analysis were retrospectively analyzed, along with karyotyping, clinical features, and follow-up. RESULTS: Eight cases with 17p13.3 CNVs consisted of five fetuses, one aborted embryo and two probands manifested severe congenital defects. The indications of prenatal testing varied considerably for the five fetuses, including ultrasound abnormalities (n = 3), segmental deletions indicated by non-invasive prenatal testing (n = 1), and intellectual disability in the mother of one fetus (n = 1). Of them, two and six harbored copy number gains and losses involving 17p13.3, respectively. The size of the detected 17p13.3 CNVs ranged from 576 kb to 5.7 Mb. Case 1 was diagnosed with 17p13.3 duplication syndrome, and cases 4, 6, and 7 with Miller-Dieker syndrome (MDS). Microdeletions of the 17p13.3 region in two cases (cases 5 and 8) involving YWHAE and CRK, sparing PAFAH1B1, were classified as pathogenic. Case 2 harbored a 576 kb microduplication, encompassing YWHAE and CRK but not PAFAH1B1, which was of maternal origin and considered a variant of uncertain significance. Case 3 carried one 74.2 Mb mosaic duplication of approximately 3.5 on chromosome 17p13.2q25.3, and two deletions at 17p13.3p13.2 and 17q25.3. The karyotype of case 3 was 46,XY,r(17)(p13q25). For five fetuses, only case 2 continued gestation and showed normal development at the age of 15 months; the others were subjected to termination of pregnancy. CONCLUSION: The clinical findings of 17p13.3 microdeletions or microduplications varied among subjects, and 17p13.3 CNVs often differ in size and gene content. Microdeletions or microduplications containing the typical MDS region, as well as the microdeletions involving YWHAE and CRK, could be classified as pathogenic. The clinical significance of small duplications including YWHAE and CRK but not PAFAH1B1 remains uncertain, for which parental testing and clinical heterogeneity should be considered in genetic counseling.

Positive predictive value of noninvasive prenatal testing for sex chromosome abnormalities.

BACKGROUND: Early and intermediate serological screening cannot detect sex chromosome abnormalities. Currently, noninvasive prenatal testing (NIPT) is the only procedure available for screening such disorders; however, its use is controversial. METHODS AND RESULTS: A total of 47,855 pregnant women underwent NIPT at our referral center from January 2014 to December 2020. Of the 314 patients with a positive NIPT indicating sex chromosome abnormalities, 260 were screened via karyotype analysis and single nucleotide polymorphism (SNP) array after amniotic fluid extraction; 96 cases were confirmed. Karyotype analysis and SNP array were consistent in the diagnosis of 88 out of the 96 fetuses. The positive predictive value (PPV) for sex chromosome abnormalities was found to be 36.9%. The PPV in patients aged 30-34 years was significantly higher than that in patients aged < 30 years. No statistically significant difference was observed on the PPV among patients with or without previous adverse pregnancy outcomes. Moreover, 83 women carrying fetuses were diagnosed with a sex chromosome abnormality terminated their pregnancy. CONCLUSIONS: Improvements in detection and analytical technologies are needed to increase the accuracy of sex chromosome abnormalities detection. Pregnant women with a positive NIPT for these abnormalities may require invasive diagnostic procedures such as karyotype analysis and SNP array for better genetic counseling.

Paternal uniparental disomy of chromosome 16 resulting in homozygosity of a GPT2 mutation causes intellectual and developmental disability.

Recessive mutations in glutamate pyruvate transaminase 2 (GPT2) have recently been found to be associated with intellectual and developmental disability (IDD). In this study, we discovered a homozygous missense variant, NM_133443: [c.1172C > T, p. Pro391Leu], of GPT2 on chromosome 16 in a proband diagnosed with IDD through trio whole-exome sequencing (WES). The pathogenicity of the variant was further verified by bioinformatics analysis and functional studies in vitro. This autosomal recessive disease was caused by paternal uniparental disomy (UPD) which was further proven by single nucleotide polymorphism array (SNP array). In past literature, recessive diseases in chromosome 16 were usually due to maternal UPD where Mendel's law of inheritance was not applicable. However, in our case we found that paternal UPD can cause recessive diseases related to the GPT2 gene on chromosome 16. Our study provides an important line of evidence for the diagnosis of GPT2-related intellectual developmental disorders.

Single nucleotide polymorphism array in genetic evaluation of fetal ultrasound abnormalities: a retrospective follow-up study.

Fetal ultrasound abnormalities may be complicated by cognitive dysfunction or developmental retardation, and ultrasonography cannot detect these problems; therefore, chromosome detection is required in fetuses with ultrasound abnormalities. To examine the effectiveness of single nucleotide polymorphism (SNP) array in genetic diagnosis of fetal ultrasound abnormalities, the prenatal samples of 805 pregnant women with fetal ultrasound abnormalities were collected for SNP array and karyotyping analysis. A 95.5% percentage of normal karyotypes and 4.5% percentage of abnormal karyotypes were observed, and aneuploidy was detected in 28 fetuses with abnormal karyotypes. SNP array identified 89 positives, including 55 cases (6.8%) with pathogenic copy number variation (CNVs) and 34 (4.2%) with variants of unknown significance (VOUS). In addition to 36 cases showing consistent results with karyotyping, SNP array detected 19 additional cases with pathogenic CNVs, including microdeletion/microduplication syndromes in 18 cases and uniparental disomy in one case. The detection rate of pathogenic CNVs was highest in fetuses with structural abnormalities of multiple systems complicated by non-structural abnormalities (13.7%) and lowest in those with structural abnormalities of a single system (4.2%). Presence of pathogenic CNVs was 12.2% in fetuses with structural abnormalities in the urinary system, followed by in the skeletal system (10.3%), while no pathogenic CNVs were identified in fetuses with structural abnormalities in the head and face, the respiratory system or the digestive system. An 89.6% follow-up rate was seen in the study sample, and 55 fetuses with pathogenic CNVs identified by SNP array were all given induction of labor. Our data demonstrate that SNP array improves the detection of genetics aberrations in fetuses with prenatal ultrasound abnormality relative to karyotyping.

The inconsistency between two major aneuploidy-screening platforms-single-nucleotide polymorphism array and next-generation sequencing-in the detection of embryo mosaicism.

BACKGROUND: In preimplantation genetic testing for aneuploidy (PGT-A), appropriate evaluation of mosaic embryos is important because of the adverse implications of transferring embryos with high-level mosaicism or discarding those with low-level mosaicism. Despite the availability of multiple reliable techniques for PGT-A, data comparing the detection of mosaicism using these techniques are scarce. To address this gap in the literature, we compared the detection ability of the two most commonly used PGT-A platforms, next-generation sequencing (NGS) and the single-nucleotide polymorphism (SNP) array, for mosaic embryos. RESULTS: We retrospectively reviewed the data of PGT-A or preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) conducted at our center from January 2018 to October 2020, and selected blastocysts that underwent aneuploidy screening with both an SNP array and NGS. Trophectoderm biopsy, multiple displacement amplification (MDA), and aneuploidy screening with an SNP array were conducted on the enrolled blastocysts. When the SNP array indicated mosaicism, NGS was performed on the corresponding MDA product for verification. Among the 105 blastocysts diagnosed with mosaicism with the SNP array, 80 (76.19%) showed mosaicism in NGS, with complete and partial concordance rates of 47.62% (50/105) and 18.10% (19/105), respectively. The complete discordance rate of the two platforms was 34.29% (36/105). That is, 10.48% (11/105) of the blastocysts were diagnosed with completely different types of mosaicism with the two platforms, while 13.33% (14/105) and 10.48% (11/105) of the embryos diagnosed as showing mosaicism with SNP were detected as showing aneuploidy and euploidy with NGS, respectively. CONCLUSIONS: The consistency of NGS and the SNP array in the diagnosis of embryo mosaicism is extremely low, indicating the need for larger and well-designed studies to determine which platform is more accurate in detecting mosaic embryos.

Patients with polyclonal hepatocellular carcinoma are at a high risk of early recurrence and have a poor recurrence-free survival period.

BACKGROUND/PURPOSE OF THE STUDY: Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity. We hypothesized and evaluated that the CC number in hepatocellular carcinoma (HCC) tissues might be associated with the clinical outcomes of patients. METHODS: Somatic mutation, whole transcriptome, and CC number based on copy number variations of 36 frozen tissue samples of operably resected HCC tissues were analyzed by targeted deep sequencing, transcriptome analysis, and SNP array. RESULTS: The samples were classified into the heterogeneous tumors as poly-CC (n = 26) and the homogeneous tumors as mono-CC (n = 8). The patients with poly-CC had a higher rate of early recurrence and a significantly shorter recurrence-free survival period than the mono-CC patients (7.0 months vs. not reached, p = 0.0084). No differences in pathogenic non-synonymous mutations, such as TP53, were observed between the two groups when targeted deep sequencing was applied. A transcriptome analysis showed that cell cycle-related pathways were enriched in the poly-CC tumors, compared to the mono-CC tumors. Poly-CC HCC is highly proliferative and has a high risk of early recurrence. CONCLUSION: CC is a possible candidate biomarker for predicting the risk of early postoperative recurrence and warrants further investigation.

SoySNP618K array: A high-resolution single nucleotide polymorphism platform as a valuable genomic resource for soybean genetics and breeding.

Innovations in genomics have enabled the development of low-cost, high-resolution, single nucleotide polymorphism (SNP) genotyping arrays that accelerate breeding progress and support basic research in crop science. Here, we developed and validated the SoySNP618K array (618,888 SNPs) for the important crop soybean. The SNPs were selected from whole-genome resequencing data containing 2,214 diverse soybean accessions; 29.34% of the SNPs mapped to genic regions representing 86.85% of the 56,044 annotated high-confidence genes. Identity-by-state analyses of 318 soybeans revealed 17 redundant accessions, highlighting the potential of the SoySNP618K array in supporting gene bank management. The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data, suggesting that the ascertainment bias in the SoySNP618K array was largely compensated for. Genome-wide association mapping in combination with reported quantitative trait loci enabled fine-mapping of genes known to influence flowering time, E2 and GmPRR3b, and of a new candidate gene, GmVIP5. Moreover, genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate (>0.65). Thus, the SoySNP618K array is a valuable genomic tool that can be used to address many questions in applied breeding, germplasm management, and basic crop research.

Analysis of somatic copy number alterations in biliary tract carcinoma using a single nucleotide polymorphism array.

AIM: Biliary tract carcinoma (BTC), including gall bladder carcinoma (GBC) and biliary duct carcinoma (BDC), has a poor prognosis. Comprehensive genomic profiling has important roles in evaluation of the carcinogenesis of BTC. MATERIALS & METHODS: We examined somatic copy number alterations (SCNAs) using a single nucleotide polymorphism array system to analyze 36 BTC samples (11 GBCs and 25 BDCs). RESULTS: In hierarchical cluster analysis, two clusters were identified (subgroup 1 with low SCNAs and subgroup 2 with high SCNAs). GBC was predominant in subgroup 1, whereas BDC was predominant in subgroup 2, suggesting that GBC and BDC had different genetic backgrounds in terms of SCNAs. CONCLUSION: These findings could be helpful for establishing the molecular carcinogenesis of BTCs.

Myelodysplastic syndrome presenting with central diabetes insipidus is associated with monosomy 7, visible or hidden: report of two cases and literature review.

BACKGROUND: Central diabetes insipidus (CDI) is a rare complication of myelodysplastic syndrome (MDS). Although the cytogenetic features of patients with MDS and CDI are not clear, CDI in patients with acute myeloid leukemia (AML) is associated with chromosome 7 and/or 3 anomalies. CASE PRESENTATION: In this report, we describe two patients with MDS and concurrent CDI, and in one of them, CDI was the first manifestation. One patient had monosomy 7 on metaphase cytogenetics (MC). Monosomy 7 and numerous cytogenetic abnormalities were found in the other patient using single-nucleotide polymorphism array (SNP-A) karyotyping, while the MC did not uncover monosomy 7. In this manuscript we also reviewed reported cases of MDS with diabetes insipidus (DI-MDS) to summarize the relationship between DI-MDS and karyotype, and explore the best treatment strategy for DI-MDS. CONCLUSIONS: DI-MDS is closely related to monosomy 7. Allogeneic hematopoietic stem cell transplantation may be the only effective treatment for DI-MDS. The SNP-A-based karyotyping is helpful to reveal subtle cytogenetic abnormalities and unveil their roles in the clinical features of MDS.