A high degree of chromosomal instability at 13q14 in cutaneous squamous cell carcinomas: indication for a role of a tumour suppressor gene other thanRb

Background/Aims-Loss of function of the retinoblastoma (Rb) tumour suppress or gene, located on chromosome 13, is common in many inherited and sporadic forms of cancer. Inactivation of its gene product by oncogenic human papil lomaviruses (HPV) plays a key role in the genesis of cervical cancer. It ha s been shown previously that non-melanoma skin cancers of renal transplant recipients and immunocompetent patients with skin cancer also frequently ha rbour potentially oncogenic HPV types. This study aimed to examine the inte grity of the Rb gene in histologically confirmed squamous cell carcinomas ( SCCs) from renal transplant recipients and immunocompetent patients with sk in cancer. Methods-Loss of heterozygosity (LOH) at the Rb locus was examined in 13 his tologically confirmed SCCs using the D13S153 microsatellite marker, which i s located in exon 2 of the Rb gene. Loss of a second marker, D13S118, dista l telomerically to the Rb gene at 13q14.3 was also analysed. Results-Of the 13 HPV associated SCCs examined 11 were informative (two SCC s were homozygous for both microsatellite markers). LOH at the D13S153 locu s was found in four of the 10 informative SCCs and LOH at the D13S118 locus was found in five of the 11 informative cases. Overall, seven of the 11 in formative cases showed LOH at one or other locus. This represents a high de gree of chromosomal instability in these tumours. The expression off the Rb gene product in the 11 informative cases was analysed immunohistochemicall y. Expression of Rb was detected in 10 of the 11 SCCs examined. No correlat ion between the HPV status of the tumours and the expression of Rb was foun d. Although the only SCC not to express Rb also demonstrated LOH at the D13 S153 locus, the remaining SCCs that had LOH at 13q14 were able to express R b. Conclusion-Another tumour suppressor gene located at 13q14 might be respons ible for the genesis of these tumours.