Amplification at chromosome 11q13 in transitional cell tumours of the bladder

Abstract

Amplification of several markers which map to chromosome 11q13 was detected by Southern blotting in transitional cell tumours of the urinary bladder. The oncogenes INT2 and HST and the BCL1 locus were co-amplified in 20/97 (20.6%) tumours and the locus-specific minisatellite probe pMS51 (D11S97) detected amplification in 17/97 (17.5%) tumours. The high frequency of heterozygosity (greater than 70%) detected by this latter probe on HaeIII-digested DNAs provided a sensitive means to measure low levels of gene amplification (2-fold) by comparing signals obtained from each allele. A number of probes which map to 11q were used in an attempt to map the region of amplification more precisely. PGA, PGR, STMY, D11Z1 and D11S149 were not amplified in any tumours studied. SEA was amplified in 1/59 tumours and D11S146 in 12/89 tumours. A comparison of the patterns of co-amplification of individual markers in this series of tumours revealed that of the 23 tumours with amplification at this site, 11 had co-amplification of D11S97, D11S146, BCL1, INT2 and HST, 3 had co-amplification of D11S97, BCL1, INT2 and HST, 6 had co-amplification of BCL1, INT2 and HST, 1 had co-amplification of D11S97 and D11S146 and 2 had amplification of D11S97 alone. Based on available linkage data for these markers, this suggests that a putative target gene within this amplicon lies centromeric to BCL1. Amplification at 11q13 showed no correlation with tumour grade or with HER2 amplification.