Chromosome 4 deletions are frequent in invasive cervical cancer and differ between histologic variants

Objective. Patterns of discontinuous deletion of chromosome 4 have been described in histologic variants of lung carcinomas and may represent different 'hotspot' targets for gene-environment interactions. Since similar environmental risks exist for cervical cancer, we investigated patterns of discontinuous deletion in two major histologic variants. Methods. Thirteen archival cases of squamous cell cancer (SCCA) and 11 cases of adenocarcinoma (AC) were precisely microdissected. Matched normal and tumor DNA were used for polymerase chain reaction (PCR) based loss of heterozygosity (LOH) analyses using 19 polymorphic markers spanning chromosome 4. Human papillomavirus (HPV) detection was determined by PCR using general and type-specific primers (HPV 16, 18). Differences in LOH between histologic tumor types and chromosomal regions were determined using Fisher's exact test. Results. Loss at any chromosome 4 locus occurred in 92% of all tumors studied, with the majority of deletions occurring on the long arm of the chromosome. Four discrete minimal regions of discontinuous deletion (R) were identified. For these regions, LOH frequencies were 76% (R1, 4q34-q35), 48% (R2, 4q25-q26), 36% (R3, 4p15.1-p15.3), and 26% (R4, 4p16). Loss in SCCA predominated at 4q (4q34-q35; 83%) and in AC at 4p (4p15.3; 50%). Overall LOH on the p arm was significant in AC (82%) compared to SCCA (31%) (P = 0.02). HPV detection was similar in SCCA (85%) and AC (73%), and HPV 16/18 subtypes were similarly represented in both histologies. Conclusions. Chromosome 4 deletions are frequent in cervical carcinomas. Different patterns of deletion between SCCA and AC may represent gene regions targeted by different gene-environment interactions in these tumor subtypes. (C) 2000 Academic Press.