BAT-26 identifies sporadic colorectal cancers with mutator phenotype: a correlative study with clinico-pathological features and mutations in mismatch repair genes.
Microsatellite instability (MSI) is present in most colorectal cancers (CRC) associated with hereditary nonpolyposis colorectal cancer (HNPCC). MSI testing in so-called sporadic forms of CRC may become a useful tool in identifying new HNPCC kindred. The aim of this study was to analyse the utility of BAT-26 as a marker to identify CRCs with MSI and to investigate whether sporadic CRCs with MSI have a phenotypic expression similar to HNPCC cases. MSI was detected using two methods, an association of 7 poly(CA) repeats and a poly(A) repeat alone, BAT-26, in a series of 62 patients with apparently sporadic forms of CRC. Germ-line and somatic mutations in the hMSH2, hMLH1, and hMSH6 genes were analysed in patients with MSI+ tumours. Patients with MSI+ at poly(CA) loci and at BAT-26 were younger (p=0.024 and p=0.002), had tumours more frequently right sided (p=0.017 and p=0.0001) and more often mucinous (p=0.037 and p=0.005, respectively) than patients with MSI negative tumours. Mutation analysis allowed the identification of two patients carrying germ-line mutations in the hMLH1 gene (both were BAT-26+) and two other patients who had somatic mutation in the hMSH2 and in hMLH1 genes. In conclusion, the detection of MSI using poly(CA) repeats or BAT-26 alone allowed the identification of a subset of patients with clinico-pathological characteristics similar to those associated to HNPCC. BAT-26 has the advantage of being a simple and less expensive method that might be used as a screening procedure before mutation analysis.
Serviço de Gastrenterologia, Instituto Português de Oncologia Francisco Gentil, 1093 Lisboa Codex, Portugal. mcravo.cplancha@mail.telepac.pt
M
M
Cravo
P
P
Lage
C
C
Albuquerque
P
P
Chaves
I
I
Claro
T
T
Gomes
C
C
Gaspar
P
P
Fidalgo
J
J
Soares
C
C
Nobre-Leitão
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype
D014408:Biomarkers, Tumor