Fong K M, Zimmerman P V, Smith P J
Queensland Cancer Fund Research Unit, Department of Pathology, University of Queensland Medical School, Herston, Australia.
Genes Chromosomes Cancer. 1994 Jul;10(3):183-9. doi: 10.1002/gcc.2870100306.
Loss of heterozygosity (LOH) affecting loci at 11p13 and 11p15 occurs in childhood and adult carcinomas, including non-small cell lung cancer (NSCLC). In NSCLC, the highest reported frequency of LOH was 72% at the 11p13 catalase (CAT) locus. As this locus is centromeric to the Wilms' tumour (WT1) locus, possible involvement of WT1 in the pathogenesis of NSCLC was considered. We thus examined 101 cases of NSCLC for LOH at the WT1 and five other polymorphic loci along 11p. At 11p13, the frequencies of LOH were 20% (9/46) at the FSHB locus, 9% (5/53) at the WT1 locus, and 15% (6/41) at the CAT locus. The shortest region of overlap (SRO) at 11p13 was mapped centromeric to, but excluding, the WT1 locus. Only adenocarcinomas showed LOH in this region. At 11p15, LOH affected 23% (18/77) of informative cases, with the highest frequency of 36% at the insulin (INS) locus. The SRO at 11p15 was mapped telomeric to the RRM1 locus. A third region, at 11p13-15 between WT1 and RRM1, was also affected by LOH. LOH at 11p correlated significantly with advanced T stage and nodal involvement in NSCLC tumours. In the squamous cell carcinoma subtype, LOH along 11p also correlated with nodal involvement. Furthermore, squamous tumours with LOH involving 11p13 loci had significantly worse survival than those without LOH. These data suggest that tumor suppressor gene(s) on 11p affect the progression of NSCLC, particularly squamous cell carcinomas.
杂合性缺失（LOH）影响11p13和11p15位点，见于儿童和成人癌症，包括非小细胞肺癌（NSCLC）。在NSCLC中，11p13过氧化氢酶（CAT）位点报道的LOH最高频率为72%。由于该位点位于威尔姆斯瘤（WT1）位点的着丝粒侧，因此考虑WT1可能参与NSCLC的发病机制。我们因此检测了101例NSCLC患者11p上WT1及其他5个多态性位点的LOH情况。在11p13，FSHB位点的LOH频率为20%（9/46），WT1位点为9%（5/53），CAT位点为15%（6/41）。11p13的最短重叠区域（SRO）定位于WT1位点的着丝粒侧，但不包括WT1位点。仅腺癌在此区域出现LOH。在11p15，LOH影响了23%（18/77）的信息病例，胰岛素（INS）位点的频率最高，为36%。11p15的SRO定位于RRM1位点的端粒侧。WT1和RRM1之间11p13 - 15的第三个区域也受LOH影响。11p的LOH与NSCLC肿瘤的晚期T分期和淋巴结受累显著相关。在鳞状细胞癌亚型中，11p的LOH也与淋巴结受累相关。此外，11p13位点出现LOH的鳞状肿瘤患者的生存率明显低于无LOH者。这些数据表明，11p上的肿瘤抑制基因影响NSCLC的进展，尤其是鳞状细胞癌。
