Depending on the cohort, mutation detection rates vary from 70 to 90%, with most mutations located in the 3′ coding region of the gene [ 16, 17].
Of note, the mutation rate of these genes per biopsy core (rather than per tumor) is more similar to the above mentioned cohort mutation rates (13%and13%3%, respectively).
A number of other studies have investigated the penetrance of these mutations, and risks have been found to vary by birth cohort, mutation position in the gene, ascertainment criteria and population studied [ 1- 13].
In the Leeds GC cohort, mutation pre-screening using high-resolution melting technology followed by Sanger sequencing was used to detect KRAS codons 12, 13, 61 and BRAF codon 600 mutations as described in detail previously (Kramer et al, 2009; Heideman et al, 2012).
By combining MSS patients from both cohorts, mutation(s) in the five-gene signature were significantly associated with better survival, indicating that the survival advantage of signature-mutant patients was not secondary to MSI (p=0.0057; figure 5E).
In this cohort, TUBA1A mutations represent the major cause of microlissencephaly, although TUBB2B and TUBB3 mutations may also be found.
In our cohort, seven mutations in NTRK1 were found, of which one was a novel homozygous missense mutation (c.1697G>A; p.Arg565Gln) in Patient CMT-841.01 (Tables 1 and 2).
Cohort specific mutations in the growth hormone (GH1) and growth hormone-releasing hormone receptor (GHRHR) genes have been reported worldwide in isolated growth hormone deficiency (IGHD) patients.
In the present cohort, two mutations, Y604F and D661Y, were found in the SH2 domains of the STAT3 gene.
In the Yokohama GC cohort, KRAS mutations were more frequent in the elderly patients aged ⩾70 years (P=0.034).
