Wiest J S, Franklin W A, Otstot J T, Forbey K, Varella-Garcia M, Rao K, Drabkin H, Gemmill R, Ahrent S, Sidransky D, Saccomanno G, Fountain J W, Anderson M W
St. Mary's Hospital Cancer Research Institute, Grand Junction, Colorado 81502, USA.
Cancer Res. 1997 Jan 1;57(1):1-6.
Cytogenetic and molecular studies have implied the presence of tumor suppressor genes (TSGs) on chromosome 9p that are critical in the development of lung and other cancers. The p16/CDKN2 gene, a cyclin dependent kinase inhibitor, is a well-defined TSG on 9p21. Although the frequency of mutations in the p16/CDKN2 gene has been detected in approximately 30% of non-small cell lung cancer, loss of heterozygosity on 9p has been observed in greater than 70% of non-small cell lung cancers. These and other deletion mapping studies have suggested the existence of additional TSGs on 9p. This study examined chromosome 9p for TSG loci by analyzing 23 squamous cell carcinomas of the lung with 21 microsatellite markers. Loss of heterozygosity was detected in all of the tumors, and homozygous deletions of the p16/ CDKN2 locus were observed in 6 of the 23 tumors (26%). In addition, a novel region of homozygous deletion was detected in six tumors (26%) at D9S126, approximately 2.5 cM proximal to p16/CDKN2. A single tumor contained a homozygous deletion at both the p16/CDKN2 locus and the D9S126 locus. The possibility of homozygous loss was confirmed by multiplex PCR using both the D9S126 marker and a chromosome 9p control marker. Fluorescence in situ hybridization analysis with P1 and cosmid probes containing D9S126 also confirmed these data. The minimum region of homozygous deletion was determined by testing markers immediately proximal and distal to the D9S126 region. The data identify a homozygous loss on the short arm of chromosome 9 suggesting the presence of a novel TSG locus, proximal to p16/CDKN2 and located between D9S265 and D9S259.
细胞遗传学和分子研究表明，9号染色体短臂上存在肿瘤抑制基因（TSG），这些基因在肺癌和其他癌症的发生发展中起关键作用。p16/CDKN2基因是一种细胞周期蛋白依赖性激酶抑制剂，是9p21上一个明确的TSG。虽然在大约30%的非小细胞肺癌中检测到了p16/CDKN2基因的突变，但在超过70%的非小细胞肺癌中观察到了9p杂合性缺失。这些以及其他缺失定位研究表明9p上存在额外的TSG。本研究通过分析23例肺鳞状细胞癌和21个微卫星标记来检测9号染色体短臂上的TSG位点。在所有肿瘤中均检测到杂合性缺失，23例肿瘤中有6例（26%）观察到p16/CDKN2位点的纯合缺失。此外，在6例肿瘤（26%）中检测到一个新的纯合缺失区域，位于D9S126，距离p16/CDKN2约2.5厘摩近端。单个肿瘤在p16/CDKN2位点和D9S126位点均存在纯合缺失。使用D9S126标记和9号染色体短臂对照标记进行多重PCR证实了纯合缺失的可能性。用包含D9S126的P1和黏粒探针进行荧光原位杂交分析也证实了这些数据。通过检测D9S126区域近端和远端的标记确定了纯合缺失的最小区域。数据表明9号染色体短臂上存在纯合缺失，提示存在一个新的TSG位点，位于p16/CDKN2近端，在D9S265和D9S259之间。
