Singh B, Lim D, Cigudosa J C, Ghossein R, Shaha A R, Poluri A, Wreesmann V B, Tuttle M, Shah J P, Rao P H
Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Surgery. 2000 Dec;128(6):888-93;discussion 893-4. doi: 10.1067/msy.2000.110847.
Determination of the genetic composition of papillary thyroid cancers may help explain differences in observed clinical behavior. Comparative genomic hybridization (CGH) is a novel molecular cytogenetic assay that allows simultaneous detection of gains, losses, and amplification of genetic information, making it an ideal screening tool. The aim of this study was to identify genetic aberrations occurring in papillary thyroid cancers by using CGH analysis.
CGH analysis was performed on 21 individual cases of papillary thyroid cancers. Nonparametric statistical comparisons were performed with the Fisher exact test.
Genetic abnormalities were identified by CGH in 10 of 21 cases (48%). A recurrent pattern of aberrations was seen in cases where genetic changes were detected, involving losses at chromosome arms 1p and 9q and chromosomes 17, 19, and 22, and gains at chromosome 4 and chromosome arms 5q, 6q, 9q, and 13q. The loss of chromosome 22 was unique to younger patients (P =.05) and was associated with a higher rate of regional lymphatic metastasis (19% vs 80%, P =.02).
Two genetically unique groups of patients were identified by using CGH analysis. One group had no detectable aberrations; the other had a recurrent pattern of aberrations, localizing to the identical chromosomal loci. This pattern of aberrations suggests that the involved loci may contain genes important in thyroid carcinogenesis. The clinical significance of the presence of copy number changes detected by CGH needs to be determined. In addition, molecular cloning of involved genes in each of the aberrations is warranted.
确定甲状腺乳头状癌的基因组成可能有助于解释所观察到的临床行为差异。比较基因组杂交（CGH）是一种新型分子细胞遗传学检测方法，可同时检测基因信息的增加、缺失和扩增，使其成为一种理想的筛查工具。本研究的目的是通过CGH分析鉴定甲状腺乳头状癌中发生的基因畸变。
对21例甲状腺乳头状癌个体病例进行CGH分析。采用Fisher精确检验进行非参数统计比较。
21例病例中有10例（48%）通过CGH鉴定出基因异常。在检测到基因变化的病例中观察到一种反复出现的畸变模式，包括1号染色体短臂和9号染色体长臂以及17、19和22号染色体的缺失，以及4号染色体和5号染色体长臂、6号染色体长臂、9号染色体长臂和13号染色体长臂的增加。22号染色体的缺失在年轻患者中是独特的（P = 0.05），并且与区域淋巴结转移率较高相关（19%对80%，P = 0.02）。
通过CGH分析鉴定出两组基因独特的患者。一组没有可检测到的畸变；另一组有反复出现的畸变模式，定位于相同的染色体位点。这种畸变模式表明所涉及的位点可能包含在甲状腺癌发生中起重要作用的基因。需要确定CGH检测到的拷贝数变化存在的临床意义。此外，对每个畸变中涉及的基因进行分子克隆是必要的。
