Insertion of an Alu-like element in MLH1 intron 7 as a novel cause of Lynch syndrome Journal Article
| Authors: | Li, Y.; Salo-Mullen, E.; Varghese, A.; Trottier, M.; Stadler, Z. K.; Zhang, L. |
| Article Title: | Insertion of an Alu-like element in MLH1 intron 7 as a novel cause of Lynch syndrome |
| Abstract: | Background: Lynch Syndrome (LS) is caused by germline mutations in the DNA mismatch repair (MMR) genes with mutations in MLH1 accounting for ~40% of LS-related alterations. Methods: MSK-IMPACT analysis was performed on peripheral blood from a patient with early- onset colorectal cancer. Subsequently PCR and sequencing was performed to characterize the insertion. Immunohistochemistry for MMR genes and MLH1 promoter methylation were analyzed on patient's tumor. Results: MSK-IMPACT germline testing revealed an insertion into c.588+8_588+9 of MLH1 intron 7. The insertion was further characterized as an AluSx-like element with ~115 bp in length. Functional studies demonstrated that the AluSx-like element led to complete disruption of mRNA splicing and probably resulted in transcriptional termination at the poly (A) region of the AluSx-like insertion. Conclusions: The insertion of a truncated AluSx like element into MLH1 intron 7 results in aberrant splicing and transcription, thereby causing Lynch syndrome. This study confirms that retrotransposon insertions may be an important mechanism for cancer predisposition. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. |
| Keywords: | lynch syndrome; splicing; mlh1; alusx |
| Journal Title: | Molecular Genetics and Genomic Medicine |
| Volume: | 8 |
| Issue: | 12 |
| ISSN: | 2324-9269 |
| Publisher: | John Wiley & Sons Ltd. |
| Date Published: | 2020-12-01 |
| Start Page: | e1523 |
| Language: | English |
| DOI: | 10.1002/mgg3.1523 |
| PROVIDER: | scopus |
| PMCID: | PMC7767547 |
| PUBMED: | 33058565 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 January 2021 -- Source: Scopus |
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