title: Low somatic K-ras mutation frequency in colorectal cancer diagnosed under the age of 45 years.
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.
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Vic., Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Alsop
authors.forename: Leeanne
authors.initials: L
authors.lastname: Mead
authors.forename: Letitia D
authors.initials: LD
authors.lastname: Smith
authors.forename: Simon G
authors.initials: SG
authors.lastname: Royce
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Tesoriero
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
authors.forename: Andrew
authors.initials: A
authors.lastname: Haydon
authors.forename: Garry
authors.initials: G
authors.lastname: Grubb
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
mesh_terms: D000328:Adult; D000367:Age Factors; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation / Q000235:genetics*