Two novel regions of interstitial deletion on chromosome 8p in colorectal cancer

We have investigated interstitial deletions of chromosome 8 in 70 colorecta l carcinomas and 11 colonic adenomas using 11 microsatellite markers, inclu ding eight spanning the centromeric region of chromosome 8p (p11.2-p12). Al lelic loss or imbalance was observed in 38 (54%) cancers and four (36%) ade nomas, Twenty-eight (40%) of the cancers had deletions of 8p11.2-p12. Two d istinct and independent regions of interstitial loss were found within this region. Fluorescent in situ hybridization, using an alpha! satellite repea t probe to the centromere of 8p and two probes to the P1 region, was perfor med in four tumours that demonstrated allelic imbalance. Localized heterozy gous deletions were confirmed in all four tumours, Eleven (16%) cancers had localized deletion in the region ANK-1 to D8S255 (P1) and a further eleven (16%) cancers had a less well localized deletion in the region defined by the markers D8S87 to D8S259 (P2), Loss of both centromeric loci was identif ied in a further six (9%) tumours, A functional significance for these two deletion regions was sought by correlation with primary and secondary tumou r characteristics. Isolated P2 deletion was associated with 'early' T1 canc ers (2p = 0.0002), and were also identified in 3/11 adenomas, Conversely, i nterstitial deletions of the P1 locus were more frequently seen in 'locally invasive' T3/4 cancers (2p = 0.015), and isolated P1 deletions were also a ssociated with the presence of liver metastases (2p = 0.016). Our data prov ide evidence of at least two genes within the 8p11.2-p12 region, mutations in which may confer different and independent roles in the pathogenesis of colorectal cancer.