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Insertion of an SVA element in MSH2 as a novel cause of Lynch syndrome
Author(s) -
Yang Ciyu,
Li Yirong,
Trottier Magan,
Farrell Michael P.,
Rai Vikas K.,
SaloMullen Erin,
Gallagher David J.,
Stadler Zsofia K.,
van der Klift Heleen M.,
Zhang Liying
Publication year - 2021
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22950
Subject(s) - msh2 , lynch syndrome , genetics , dna mismatch repair , exon , retrotransposon , biology , alu element , palb2 , gene , germline mutation , microbiology and biotechnology , mutation , dna repair , transposable element , genome , human genome
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.