Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C--T:A mutations

Autor: Jacqueline M. Best, Sheila Jordan, Julian R. Sampson, G. T. Williams, Jeremy Peter Cheadle, Paul Emmerson, Sian D. Jones, Julie Helen Maynard
Rok vydání: 2002
Předmět:
Zdroj: Human molecular genetics. 11(23)
ISSN: 0964-6906
Popis: We have recently demonstrated that inherited defects of the base excision repair gene MYH predispose to multiple colorectal adenomas and carcinoma.Three affected siblings from a single British family were identified as Y165C/G382D compound heterozygotes and both missense mutations were shown to be functionally compromised.Here, we report the identification of seven further unrelated patients with >100 colorectal adenomas (six with colorectal cancer) and biallelic germline mutations in MYH: four were homozygous for truncating mutations, two were homozygous for Y165C and one was a Y165C/G382D compound heterozygote.As predicted from studies of the bacterial and yeast orthologues of MYH, colorectal tumours from affected individuals displayed a significant excess of somatic G:C!T:A mutations in APC ,a s compared to sporadic ( v 2 ¼ 242.96, P < 10 � 20 ) or FAP-associated ( v 2 ¼ 194.85, P < 10 � 20 ) colorectal tumours. The sequence immediately downstream of the somatic G:C!T:A mutations was predominantly AA, irrespective of the nature of the germline MYH mutations.These findings confirm the role of MYH in colorectal adenoma and carcinoma predisposition.
Databáze: OpenAIRE