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Low somatic K-ras mutation frequency in colorectal cancer diagnosed under the age of 45 years.

Authors
  • Alsop, Kathryn
  • Mead, Leeanne
  • Smith, Letitia D
  • Royce, Simon G
  • Tesoriero, Andrea A
  • Young, Joanne P
  • Haydon, Andrew
  • Grubb, Garry
  • Giles, Graham G
  • Jenkins, Mark A
  • Hopper, John L
  • Southey, Melissa C
Type
Published Article
Journal
European Journal of Cancer
Publisher
Elsevier
Publication Date
Jul 01, 2006
Volume
42
Issue
10
Pages
1357–1361
Identifiers
PMID: 16765042
Source
Medline
License
Unknown

Abstract

Somatic mutation of K-ras is known to be a common event in colorectal cancer tumourigenesis however its association with age at onset has not been widely explored. In this study, we have analyzed tumours from a population-based study of colorectal cancer diagnosed before the age of 45 years, in which cases had been previously screened for germ-line mismatch repair gene mutations and for microsatellite instability. We used a micro-dissection and sequencing approach to search for somatic K-ras mutations in codons 12, 13 and 61 in 101 early-onset colorectal cancers. Six (6%) somatic K-ras mutations were detected; five in codon 12 (4 G>T transitions and 1 G>A) and one in codon 13 (G>A transition). All codon 12 mutations were identified in microsatellite stable tumours and the codon 13 mutation was identified in a MSI-high tumour. Four cases with K-ras mutations had no reported family history of colorectal cancer and two had some family history of colorectal cancer. None were known to carry a germ-line mutation in hMSH2, hMLH1, hMSH6 or hPMS2. The role of somatic K-ras mutations in early-onset colorectal cancer carcinogenesis appears to be minor, in contrast to its significant role in colorectal cancer of later age of onset.

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