Implication of the BRCA2 and putative "BRCA3" genes in Dukes' stage C, replication error-negative colon cancer.
BACKGROUND
Although BRCA genes have been implicated in certain tumors, particularly breast tumors, their role in colon tumorigenesis has not been fully explored. We aimed to investigate the association of the BRCA2 and putative "BRCA3" genes in a homogeneous series of right-sided colon cancer specimens.


METHODS
Twenty-three Dukes' stage C, replication error-negative carcinomas were selected from patients with right-sided colon cancer. After histological examination and microdissection, DNA was extracted from normal colon and carcinoma from each patient. Five microsatellite markers spanning the region of BRCA2 and BRCA3 on chromosome 13 (D13S218, D13S219, D13S165, D13S156, and D13S160) and two markers intragenic to BRCA2 and BRCA3 (D13S171 and D13S1308, respectively) were used. Polymerase chain reaction products were analyzed by using a fluorescent allele imbalance assay.


RESULTS
Markers demonstrating the highest allelic imbalance were D13S1308 (53%), D13S171 (33%), and D13S160 (37%).


CONCLUSIONS
The intragenic markers D13S1308 (BRCA3) and D13S171 (BRCA2) on chromosome 13 demonstrated a high frequency of allelic imbalance in primary colon carcinoma. This suggests an involvement of BRCA2 and putative BRCA3 in colon tumorigenesis in right-sided, replication error-negative, Dukes' stage C cancers. Further studies are needed to confirm the precise role of these genes, and any prognostic significance, in colon cancer.
Sivarajasingham
Nala S
NS
Postgraduate Medical Institute of the University of Hull in Association with the Hull-York Medical School, University of Hull, R&D Building, Castle Hill Hospital, Hull, HU16 5JQ, United Kingdom.
Cawkwell
Lynn
L
Baker
Richard P
RP
O'Kane
Sara L
SL
Smyth
Edward F
EF
Tilsed
Jonathan V T
JV
Watson
Mark B
MB
Greenman
John
J
Monson
John R T
JR
D000483:Alleles; D002882:Chromosomes, Human, Pair 13; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics; D024522:Genes, BRCA2; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm