Report of a germline double heterozygote in MSH2 and PALB2

• Published in: Molecular genetics & genomic medicine 2020-10, Vol.8 (10), p.e1242-n/a
• Main Authors: Agiannitopoulos, Konstantinos, Papadopoulou, Eirini, Tsaousis, Georgios N., Pepe, Georgia, Kampouri, Stavroula, Patsea, Eleni, Lypas, George, Nasioulas, George
• Format: Article
• Language: English
• Subjects: Age; Anemia; Bioinformatics; Breast; Breast cancer; Clinical Report; Clinical Reports; Colorectal cancer; Colorectal carcinoma; Computer applications; Copy number; Deoxyribonucleic acid; Diagnostic systems; DNA; Endometrial cancer; Endometrium; Exons; Family medical history; Genes; Genetic screening; Genetic testing; Genetics; Genomics; Heterozygotes; Investigations; Laboratories; Leukocytes; MSH2; MSH2 protein; Mutation; Next-generation sequencing; NGS; Ovarian cancer; PALB2; Pancreas; Pancreatic cancer; pathogenic variant; Prostate cancer; Proteins; Risk assessment; Siblings; Software; Surveillance; Technology assessment; Uterine cancer
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.1242

Background Carriers with pathogenic variants in MSH2 have increased risk to develop colorectal, endometrium, ovarian, and other types of cancer. The PALB2 is associated with breast, ovarian, pancreatic, and prostate cancer. We describe the case of a 42‐year‐old female diagnosed with endometrial cancer at the age of 42 years with a strong family history of colorectal cancer, which was referred to our private diagnostic laboratory for genetic testing. Methods In this study, we performed next‐generation sequencing (NGS) using an amplicon based 26 genes panel. The presence of multi‐exonic copy number variations (CNVs) was investigated by computational analysis and Multiplex Ligation‐dependent Probe Amplification (MLPA). Results A gross deletion of the genomic region encompassing exons 11–16 of the MSH2 and the loss‐of‐function variant c.757_758delCT, p.(Leu253Ilefs*3) in the PALB2 were identified in the proband. Conclusions Multigene analysis using NGS technology allows the identification of pathogenic variants in genes that would normally not be tested based on the patient diagnosis. In our case these results explained not only the personal and/or family history of cancer but also allowed the surveillance for prevention of other cancer types. Moreover, the detection of large genomic rearrangements should be routinely included in hereditary cancer testing. We describe the case of a 42‐year‐old female diagnosed with endometrial cancer with a strong family history of colorectal cancer, which was referred to our private diagnostic laboratory for genetic testing. By next‐generation sequencing (NGS) and Multiplex Ligation‐dependent Probe Amplification (MLPA) analysis we identified a gross deletion of the genomic region encompassing exons 11–16 of the MSH2 gene and the loss‐of‐function variant c.757_758delCT, p.(Leu253Ilefs*3) in the PALB2 gene in our proband.