Insertion of an SVA element in MSH2 as a novel cause of Lynch syndrome.

Autor: Yang C; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Li Y; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Trottier M; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Farrell MP; Department of Cancer Genetics, Mater Private Hospital, Dublin, Ireland., Rai VK; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., E Salo-Mullen E; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Gallagher DJ; Department of Cancer Genetics, Mater Private Hospital, Dublin, Ireland., Stadler ZK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., van der Klift HM; Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands., Zhang L; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Jazyk: angličtina
Zdroj: Genes, chromosomes & cancer [Genes Chromosomes Cancer] 2021 Aug; Vol. 60 (8), pp. 571-576. Date of Electronic Publication: 2021 Apr 21.
DOI: 10.1002/gcc.22950
Abstrakt: Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch syndrome (LS). In this study, we identified and characterized a novel SINE-VNTR-Alu (SVA) insertion in exon 12 of MSH2 in an individual with early-onset colorectal cancer and a very strong LS family history. RT-PCR analysis indicated a larger aberrant MSH2 transcript in one of the family members. MSK-IMPACT next-generation sequencing and long-range PCR analyses revealed an insertion in MSH2 exon 12 at the c.1972 position in an antisense orientation. The insertion was further characterized as an SVA element approximately 3 kb in length, belonging to the SVA_F1 family of retrotransposons. This variant also segregated with LS related cancers in four affected family members in this family. Based on this evidence, this MSH2 SVA insertion is considered pathogenic.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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