Double Trisomy 16 and 22 Clinically Mimic Partial Hydatidiform Mole in a Case of Subsequent Pregnancy Loss.

A case of double trisomy 16 and 22 in the second pregnancy loss is presented. DNA analyses (short tandem repeats genotyping) of miscarriage specimen was indicated because of ultrasound suspicion of partial hydatidiform mole. After the partial hydatidiform mole exclusion, further DNA analyses focused on the most common aneuploidies causing pregnancy loss, detected double trisomy 16 and 22 in the product of conception. The couple was referred to clinical genetic consultation and normal parental karyotypes were proved. For further explanatory purposes, archived material from the first pregnancy loss was analyzed and trisomy of chromosome 18 was detected. By comparison of allelic profiles of the mother, father, and both losses, the maternal origin of all aneuploidies was proven what can be attributed to frequent meiosis errors, probably due to advanced maternal age (44 years at the first loss and 45 years at the second loss). In conclusion, aneuploidies can mimic partial hydatidiform mole. Genetic analysis is helpful on the one hand to rule out partial hydatidiform mole and on the other hand to identify aneuploidies and in this way to determine the cause of miscarriage.

Pilot study of gene mutations associated with Lynch syndrome in Slovak patients with breast cancer.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant inherited disorder which causes an increased risk of cancer, especially colorectal and endometrial carcinomas. Recent studies have shown an association between LS and breast cancer as well. The aim of our study is to highlight the possible presence of mutations in genes associated with LS in patients with breast cancer and the need to include the examination of Lynch-associated genes in patients with a family history of breast cancer as well as in patients with recurrent breast cancer, as well as with the occurrence of other Lynch-associated cancer. MATERIALS AND METHODS: We analyzed tumor tissue samples from 78 patients with primary breast cancer. Our samples were tested with a gene panel associated with the risk of developing breast cancer, while in our study we focused primarily on the occurrence of mutations in mismatch-repair genes. DNA isolated from tumor tissue was sequenced using next generation sequencing (NGS) and analyzed using the Ingenuity Variant Analysis tool. To confirm the germline mutation, we examined the patient's blood sample using NGS sequencing. RESULTS: As a result of our analysis, we managed to identify a mutation in the PMS2 gene in one patient's breast tumor tissue. The presence of this mutation indicates that the resulting cancer may be a consequence of LS. As for pathogenicity, this was probably a pathogenic variant, as we detected deletions in the exon region, which led to frameshift mutation. Moreover, we also identified single-nucleotide pathogenic variants in the TP53 and PIK3CA genes. To definitively establish the diagnosis of LS in the patient, we examined a blood sample, where we also identified a mutation of the PMS2 gene. CONCLUSION: LS is underdiagnosed in many Lynch-associated cancers. However, in the case of a familial occurrence of breast cancer and other Lynch-associated genes, it is important to think about a possible diagnosis of LS and, if the patient meets the diagnostic criteria, to carry out a genetic examination of Lynch-associated genes.

PTEN mutations as predictive marker for the high-grade endometrial cancer development in slovak women.

Endometrial carcinoma (ECa) is one of the most common neoplasia of the female genital tract. The phosphatase and tensin (PTEN) homolog is the most frequently mutated tumor suppressor gene in endometrial carcinoma. PTEN encodes a phosphatase, a key regulatory enzyme involved in a signal transduction pathway that regulates cell growth, migration and apoptosis. The study evaluates an association between the morphological appearance of endometrial hyperplasia and ECa, and the presence of PTEN variations, PTEN protein´s level and intracellular localization. A total of 67 archived formalin-fixed and paraffin-embedded human biopsy tissue specimens with normal proliferative and secretory endometrium, endometrial hyperplasia without atypia and endometrial atypical hyperplasia, endometrioid the grade G1 and G3 and serous subtype of ECa were evaluated by sequencing for the presence of mutations in coding regions of PTEN gene of endometrial epithelial cells. The PTEN gene expression and intercellular localization of PTEN protein were evaluated immunohistochemically by immunoreactive score (IRS). PTEN mutation spectrum in endometrial carcinoma was identified for Slovak population. 28 non-silent mutations were identified in PTEN, twelve of them were novel, not annotated in Catalogue of Somatic Mutations in Cancer. Higher frequency of PTEN mutations was observed in serous carcinoma compared to global average. No correlation was observed between samples´ IRS, PTEN cellular localization and identified mutations. PTEN sequencing can be beneficial for patients considering prognosis of disease and sensitivity to treatment.

Importance of the genetics in the diagnostics of hydatidiform mole.

OBJECTIVE: To summarize the possibilities of the genetic analysis of hydatidiform moles and point out its perspectives in the diagnostics of this disease. DESIGN: Review. SETTING: Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Slovak Republic. METHODS: Analysis of published literature data from the internet databases PubMed, ScienceDirect, Scopus and printed literature from the period 1963-2019. RESULTS: This review refers on karyotyping, flow cytometry, FISH (Fluorescent in Situ Hybridization), VNTR-RFLP analysis (Variable Number of Tandem Repeats-Restriction Fragment Length Polymorphism), VNTR-PCR analysis (Variable Number of Tandem Repeats-Polymerase Chain Reaction) and STR (Short Tandem Repeat) genotyping of hydatidiform moles. The article summarizes possible application of these methods in the differential diagnostics of molar pregnancy (partial and complete hydatidiform moles) and nonmolar hydropic abortions. CONCLUSION: Genetic analyses offer precise identification of types of molar pregnancies when histopathological diagnosis is not clear during early stages of pathology.

ERVW-1 gene polymorphisms related to preeclampsia.

OBJECTIVES: Identification of genetic association between the gene ERVW-1 and preeclampsia. BACKGROUND: Preeclampsia is a multifactorial disease affecting women during pregnancy and it is one of the main causes of perinatal and maternal morbidity and mortality. The pathophysiology of preeclampsia is very complex and several aspects of the disease have not been elucidated yet. Abnormal placentation frequently occurs during severe preeclampsia. Protein syncytin 1, a product of the ERVW-1 gene, plays a crucial role in the syncytiotrophoblast differentiation and optimal placentation. The syncytin 1 expression is disturbed during preeclampsia. The main focus of this study was the analysis of the ERVW-1 regulatory regions and identification of DNA polymorphisms associated with preeclamptic cases in Slovak population. METHODS: Regulatory region of gene ERVW-1 was analyzed by sequencing to identify genetic variants. RESULTS: We identified four DNA variants, namely rs4727276, rs148592540, rs569899772 and rs555416193, in samples of Slovak population. CONCLUSION: No relation between polymorphisms and preeclampsia was observed, indicating that further investigations with a larger sampling are still required. However, our work represents new original approach in genetic differential diagnosis of preeclampsia with possible useful findings in the future (Tab. 3, Fig. 1, Ref. 34).

PTEN sequence analysis in endometrial hyperplasia and endometrial carcinoma in Slovak women.

Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.