Risk for Hereditary Neoplastic Syndromes in Women with Mismatch Repair-Proficient Endometrial Cancer.

Endometrial cancer (EC) is a prevalent malignancy in women, and those who are proficient in the DNA mismatch repair (pMMR) pathway may have a family history (FH) that meets the criteria for a hereditary neoplastic condition (HNS). This study aimed to estimate the risk of HNS in women with pMMR endometrial tumors by analyzing their FH. To achieve this, we collaborated with a primary study and collected FH information by telephone. The final sample comprised 42 women who responded to the Primary Screening Questionnaire. Their family pedigrees were drawn and categorized according to internationally standardized criteria for the risk of HNS. Results showed that 26 women (61%) were found to be at risk for HNS, with Bethesda criteria being met by 23%, Amsterdam criteria by 15%, and 4% met the attenuated familial adenomatous polyposis criteria. Our results emphasize the importance of FH and the need to encourage healthcare professionals to collect and document FH more frequently, even if it is self-reported. By identifying individuals with HNS, we can improve their outcomes and reduce the burden of cancer in families with a predisposition to cancer.

Applicability of the SNPforID 52-plex panel for human identification and ancestry evaluation in a Brazilian population sample by next-generation sequencing.

SNP analysis is of paramount importance in forensic genetics. The development of new technologies in next-generation sequencing allowed processing a large number of markers in various samples simultaneously. Although SNPs are less informative than STRs, they present lower mutation rates and perform better when using degraded samples. Some SNP systems were developed for forensic usage, such as the SNPforID 52-plex, from the SNPforID Consortium, containing 52 bi-allelic SNPs for human identification. In this paper we evaluated the informativeness of this system in a Brazilian population sample (n = 340). DNA libraries were prepared using a customized HaloPlex Target Enrichment System kit (Agilent Technologies, Inc.) and sequenced in the MiSeq Personal Sequencer platform (Illumina Inc.). The methodology presented here allowed the analysis of 51 out of 52 SNPforID markers. Allele frequencies and forensic parameters were estimated, revealing high informativeness: the combined match probability and power of exclusion were 6.48 × 10-21 and 0.9997, respectively. Population admixture analysis indicates high European contribution (more than 70%) and low Amerindian contribution (less than 10%) in our population, while individual admixture analyses were consistent with the majority of individuals presenting high European contribution. This study demonstrates that the 52-plex kit is suitable for forensic cases in a Brazilian population, presenting results comparable with those obtained using a 16 STR panel.

Extended HLA-G genetic diversity and ancestry composition in a Brazilian admixed population sample: Implications for HLA-G transcriptional control and for case-control association studies.

Human leukocyte antigen-G (HLA-G) is a nonclassical Major Histocompatibility Complex (MHC) molecule with immunomodulatory function and restricted tissue expression. The genetic diversity of HLA-G has been extensively studied in several populations, however, the segment located upstream -1406 has not yet been evaluated. We characterized the nucleotide variation and haplotype structure of an extended distal region (-2635), all exons and the 3'UTR segment of HLA-G by next-generation sequencing (NGS) in a sample of 335 Brazilian individuals. We detected 29 variants at the HLA-G distal promoter region, arranged into 19 haplotypes, among which we identified sites that may influence transcription factor targeting. Although the variation pattern in the distal region resembled the one observed in the conventional promoter segment, molecular signature for balancing selection was observed in the promoter segment from -1406 to -1 (Tajima's D = 2.315, P = 0.017), but not in this distal segment (D = 1.049, P = 0.118). Furthermore, the ancestry composition of this Brazilian population sample was determined by the analysis of SNPforID 34-plex ancestry informative marker (AIM) SNP panel. The distribution of HLA-G haplotypes was ancestry-dependent, corroborating previous findings and emphasizing the importance of considering the ancestry information in association studies.