Target gene mutational pattern in Lynch syndrome colorectal carcinomas according to tumour location and germline mutation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-08

AUTHORS

Manuela Pinheiro, Carla Pinto, Ana Peixoto, Isabel Veiga, Paula Lopes, Rui Henrique, Helena Baldaia, Fátima Carneiro, Raquel Seruca, Ian Tomlinson, Michal Kovac, Karl Heinimann, Manuel R Teixeira

ABSTRACT

BACKGROUND: We previously reported that the target genes in sporadic mismatch repair (MMR)-deficient colorectal carcinomas (CRCs) in the distal colon differ from those occurring elsewhere in the colon. This study aimed to compare the target gene mutational pattern in microsatellite instability (MSI) CRC from Lynch syndrome patients stratified by tumour location and germline mutation, as well as with that of sporadic disease. METHODS: A series of CRC from Lynch syndrome patients was analysed for MSI in genes predicted to be selective MSI targets and known to be involved in several pathways of colorectal carcinogenesis. RESULTS: The most frequently mutated genes belong to the TGF-β superfamily pathway, namely ACVR2A and TGFBR2. A significantly higher frequency of target gene mutations was observed in CRC from patients with germline mutations in MLH1 or MSH2 when compared with MSH6. Mutations in microsatellite sequences (A)7 of BMPR2 and (A)8 of MSH3 were significantly more frequent in the distal CRC. Additionally, we observed differences in MSH3 and TGFBR2 mutational frequency between Lynch syndrome and sporadic MSI CRC regarding tumour location. CONCLUSIONS: Our results indicate that the pattern of genetic changes differs in CRC depending on tumour location and between Lynch syndrome and sporadic MSI CRC, suggesting that carcinogenesis can occur by different pathways even if driven by generalised MSI. More... »

PAGES

686

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.2015.281

DOI

http://dx.doi.org/10.1038/bjc.2015.281

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023725765

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26247575


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