D'Amico D, Carbone D P, Johnson B E, Meltzer S J, Minna J D
Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas 75235-8593.
Cancer Res. 1992 Apr 1;52(7):1996-9.
Using single-strand conformation polymorphism we have found two polymorphic sites, AAC to AAT at codon 511 (exon 12) and GCT to GCG at codon 708 (exon 15), in the MCC gene. These sites and an RsaI polymorphic site in APC allowed us to study 23 human small cell lung cancer (SCLC) and 7 non-small cell lung cancer samples for allele loss. Of the 23 SCLC samples, 21 (91%) were informative for one or more of these markers, and we found allele loss in more than 80% (17 of 21). In non-small cell lung cancer samples, 5 of 7 (71%) were informative, and reduction or loss of one allele was found in 2 of 5 (40%). Seven cases were informative for both genes, loss of heterozygosity occurred for both genes in five, one retained heterozygosity for both, and one SCLC had loss of heterozygosity for APC but not for MCC. We conclude that loss of heterozygosity occurs frequently for MCC and APC in lung cancer of all histological types and is very frequent in SCLC. This suggests the presence of tumor suppressor gene(s) in the MCC/APC region of 5q21 involved in human lung cancer.
利用单链构象多态性，我们在MCC基因中发现了两个多态性位点，密码子511（外显子12）处的AAC突变为AAT，密码子708（外显子15）处的GCT突变为GCG。这些位点以及APC基因中的一个RsaI多态性位点使我们能够对23例人类小细胞肺癌（SCLC）和7例非小细胞肺癌样本进行等位基因缺失研究。在23例SCLC样本中，21例（91%）对这些标记中的一个或多个具有信息性，并且我们发现超过80%（21例中的17例）存在等位基因缺失。在非小细胞肺癌样本中，7例中有5例（71%）具有信息性，5例中有2例（40%）发现一个等位基因减少或缺失。7例样本对两个基因均具有信息性，5例两个基因均发生杂合性缺失，1例两个基因均保留杂合性，1例SCLC的APC基因发生杂合性缺失，但MCC基因未发生。我们得出结论，在所有组织学类型的肺癌中，MCC和APC基因频繁发生杂合性缺失，在SCLC中尤为常见。这表明5q21的MCC/APC区域存在参与人类肺癌的肿瘤抑制基因。
