Cytogenetic and fluorescence in situ hybridization characterization of chromosome 1 rearrangements in head and neck carcinomas delineate a target region for deletions within 1p11-1p13

Cytogenetic analyses have revealed structural rearrangements of chromosome 1 in a large fraction of head and neck carcinomas (HNCA), These aberrations frequently affect chromosomal band 1p13 and the centromeric region, the la tter often in the form of isochromosome i(lq) and whole-arm translocations. To delineate the critical region involved in rearrangements of proximal Ip , we have undertaken a more precise breakpoint mapping in 13 HNCAs, using m etaphase fluorescence ill situ hybridization with 11 yeast artificial chrom osome (YAC) clones spanning Ip, All of the tumors had chromosome 1 changes at G-banding analyses. Fluorescence in situ hybridization showed that in al most all of the cases, at least one copy of chromosome 1 was affected by ce ntromeric rearrangement. By the use of YAC clones mapped to juxtacentromeri c regions and a centromere-specific alpha-satellite probe, we detected vari able breakpoints in the whole-arm translocations. At the cytogenetic level, 1p13 rearrangements were frequent, However, molecular breakpoints within t his band varied among the HNCAs tested. The lack of consistently rearranged chromosome segments indicates that the pathogenetically important conseque nce of Ip rearrangements in HNCAs is loss and/or gain of genes outside the breakpoint regions. In an assessment of the genomic imbalances, partial or complete overrepresentation of Iq was seen in eight cases. Loss of Ip mater ial was also identified in eight cases; and in four of them, the deleted se gments were too small to be discovered by G-banding analysis. The minimal o verlapping deleted region was in the interval between YAC 959C4 (band p11-p 12) and the centromere (p10), Our findings indicate that a target region po tentially harboring tumor suppressor gene(s) crucial for HNCA is located wi thin chromosomal bands 1p11-p13.