皮肤鳞状细胞癌中13q14处高度的染色体不稳定性：提示存在除Rb以外的肿瘤抑制基因发挥作用。

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

作者信息

O'Connor D P, Kay E W, Leader M, Murphy G M, Atkins G J, Mabruk M J

机构信息

Pathology Department, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.

出版信息

Mol Pathol. 2001 Jun;54(3):165-9. doi: 10.1136/mp.54.3.165.

DOI:10.1136/mp.54.3.165

PMID:11376129

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1187056/

Abstract

BACKGROUND/AIMS: Loss of function of the retinoblastoma (Rb) tumour suppressor gene, located on chromosome 13, is common in many inherited and sporadic forms of cancer. Inactivation of its gene product by oncogenic human papillomaviruses (HPV) plays a key role in the genesis of cervical cancer. It has been shown previously that non-melanoma skin cancers of renal transplant recipients and immunocompetent patients with skin cancer also frequently harbour potentially oncogenic HPV types. This study aimed to examine the integrity of the Rb gene in histologically confirmed squamous cell carcinomas (SCCs) from renal transplant recipients and immunocompetent patients with skin cancer.

METHODS

Loss of heterozygosity (LOH) at the Rb locus was examined in 13 histologically confirmed SCCs using the D13S153 microsatellite marker, which is located in exon 2 of the Rb gene. Loss of a second marker, D13S118, distal telomerically to the Rb gene at 13q14.3 was also analysed.

RESULTS

Of the 13 HPV associated SCCs examined 11 were informative (two SCCs were homozygous for both microsatellite markers). LOH at the D13S153 locus 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 informative cases showed LOH at one or other locus. This represents a high degree of chromosomal instability in these tumours. The expression of the Rb gene product in the 11 informative cases was analysed immunohistochemically. Expression of Rb was detected in 10 of the 11 SCCs examined. No correlation between the HPV status of the tumours and the expression of Rb was found. Although the only SCC not to express Rb also demonstrated LOH at the D13S153 locus, the remaining SCCs that had LOH at 13q14 were able to express RB:

CONCLUSION

Another tumour suppressor gene located at 13q14 might be responsible for the genesis of these tumours.

摘要

背景/目的：位于13号染色体上的视网膜母细胞瘤（Rb）肿瘤抑制基因功能丧失在许多遗传性和散发性癌症中很常见。致癌性人乳头瘤病毒（HPV）使其基因产物失活在宫颈癌的发生中起关键作用。先前已表明，肾移植受者的非黑色素瘤皮肤癌以及有皮肤癌的免疫功能正常患者也经常携带潜在致癌性HPV类型。本研究旨在检测肾移植受者和有皮肤癌的免疫功能正常患者经组织学确诊的鳞状细胞癌（SCC）中Rb基因的完整性。

方法

使用位于Rb基因外显子2的D13S153微卫星标记，检测13例经组织学确诊的SCC中Rb基因座的杂合性缺失（LOH）。还分析了位于13q14.3处Rb基因远端端粒的另一个标记D13S118的缺失情况。

结果

在检测的13例HPV相关SCC中，11例信息充足（2例SCC对两个微卫星标记均为纯合子）。在10例信息充足的SCC中有4例发现D13S153基因座存在LOH，在11例信息充足的病例中有5例发现D13S118基因座存在LOH。总体而言，11例信息充足的病例中有7例在一个或另一个基因座显示LOH。这表明这些肿瘤具有高度的染色体不稳定性。对11例信息充足的病例进行免疫组织化学分析Rb基因产物的表达。在检测的11例SCC中有10例检测到Rb表达。未发现肿瘤的HPV状态与Rb表达之间存在相关性。虽然唯一未表达Rb的SCC在D13S153基因座也显示出LOH，但在13q14处有LOH的其余SCC能够表达RB。