Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G

C→T:A mutations

Kimihiko Oishi, Susanna Hofmann, George A. Diaz, Tartania Brown, Deepa G. Manwani, Lily Ng, Randy Young, Helen Vlassara, Yiannis A. Ioannou, Douglas Forrest, Bruce D. Gelb

Research output: Contribution to journalArticle

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Abstract

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, as compared to sporadic (X2 = 242.96, P< 10-20) or FAP-associated (X2 = 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.

Original languageEnglish (US)
Pages (from-to)2961-2967
Number of pages7
JournalHuman Molecular Genetics
Volume11
Issue number23
StatePublished - Nov 1 2002
Externally publishedYes

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Germ-Line Mutation
Adenoma
Colorectal Neoplasms
Mutation
Heterozygote
Missense Mutation
DNA Repair
Siblings
Yeasts
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Oishi, K., Hofmann, S., Diaz, G. A., Brown, T., Manwani, D. G., Ng, L., ... Gelb, B. D. (2002). Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G: C→T:A mutations. Human Molecular Genetics, 11(23), 2961-2967.

Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G : C→T:A mutations. / Oishi, Kimihiko; Hofmann, Susanna; Diaz, George A.; Brown, Tartania; Manwani, Deepa G.; Ng, Lily; Young, Randy; Vlassara, Helen; Ioannou, Yiannis A.; Forrest, Douglas; Gelb, Bruce D.

In: Human Molecular Genetics, Vol. 11, No. 23, 01.11.2002, p. 2961-2967.

Research output: Contribution to journalArticle

Oishi, K, Hofmann, S, Diaz, GA, Brown, T, Manwani, DG, Ng, L, Young, R, Vlassara, H, Ioannou, YA, Forrest, D & Gelb, BD 2002, 'Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G: C→T:A mutations', Human Molecular Genetics, vol. 11, no. 23, pp. 2961-2967.
Oishi, Kimihiko ; Hofmann, Susanna ; Diaz, George A. ; Brown, Tartania ; Manwani, Deepa G. ; Ng, Lily ; Young, Randy ; Vlassara, Helen ; Ioannou, Yiannis A. ; Forrest, Douglas ; Gelb, Bruce D. / Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G : C→T:A mutations. In: Human Molecular Genetics. 2002 ; Vol. 11, No. 23. pp. 2961-2967.
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