Molecular tumor testing in patients with Lynch-like syndrome reveals a de novo mosaic variant of a mismatch repair gene transmitted to offspring
Affiliations
- PMID: 32678338
- DOI: 10.1038/s41431-020-0689-6
Abstract
In Lynch-like syndrome, patients have tumors with microsatellite instability but no germline pathogenic variant in mismatch repair genes or somatic methylation of the MLH1 promoter. Identification of the mechanism that causes these tumors is crucial for guiding screening of the patients and their relatives. Double somatic hits are the usual explanation for these cases; however, we have previously reported a de novo mosaic pathogenic variant in a patient with Lynch-like syndrome. Using tumoral NGS analysis of a series of 16 patients with Lynch-like syndrome, we found six patients with double somatic hits, including one patient with mosaicism of a de novo pathogenic variant in MSH2. This variant was transmitted to the patient's offspring, which has significant implications for genetic counseling.
Similar articles
- Identification of Germline Mismatch Repair Gene Mutations in Lung Cancer Patients With Paired Tumor-Normal Next Generation Sequencing: A Retrospective Study.Front Oncol. 2019 Jun 26;9:550. doi: 10.3389/fonc.2019.00550. eCollection 2019.PMID: 31297337 Free PMC article.
- Universal screening for Lynch syndrome in endometrial cancers: frequency of germline mutations and identification of patients with Lynch-like syndrome.Hum Pathol. 2017 Dec;70:121-128. doi: 10.1016/j.humpath.2017.10.022. Epub 2017 Oct 28.PMID: 29107668
- Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome).Appl Clin Genet. 2014 Oct 6;7:183-93. doi: 10.2147/TACG.S48625. eCollection 2014.PMID: 25328415 Free PMC article. Review.
- Screening for germline mutations of MLH1, MSH2, MSH6 and PMS2 genes in Slovenian colorectal cancer patients: implications for a population specific detection strategy of Lynch syndrome.Fam Cancer. 2009;8(4):421-9. doi: 10.1007/s10689-009-9258-4. Epub 2009 Jun 13.PMID: 19526325
- Lynch Syndrome.2004 Feb 5 [updated 2018 Apr 12]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2020.PMID: 20301390 Free Books & Documents. Review.
No hay comentarios:
Publicar un comentario