Zhang J S, Nelson M, McIver B, Hay I D, Goellner J R, Grant C S, Eberhardt N L, Smith D I
Department of Laboratory Medicine and Pathology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Oncogene. 1998 Aug 13;17(6):789-93. doi: 10.1038/sj.onc.1201996.
We analysed 42 differentiated thyroid tumors including 15 follicular adenomas (FA), 13 papillary thyroid cancers (PTC) and 14 follicular thyroid carcinomas (FTC) with 13 microsatellite markers specific for the long arm of human chromosome 7 within 7q31; this region is deleted frequently in several other tumor types. Overall, 20 of the 42 samples analysed (48%) displayed LOH with one or more of the markers tested. LOH was detected most frequently (78%) in FTC, the most malignant of the thyroid tumors. A smallest common deleted region (SCDR) was defined in this tumor type flanked by markers D7S480 and D7S490. This SCDR is distinct from D7S522, the most commonly deleted locus in many other tumors, which was deleted in only one FTC. D7S522 did show LOH in two of six informative PTCs. None of the PTC and only two of the FAs showed LOH in the FTC SCDR. Since FA is considered a premalignant stage of FTC, our results suggest that inactivation of a putative tumor suppressor at 7q31.2 may be acquired during adenoma to carcinoma progression. The absence of LOH at this locus amongst PTC suggests that inactivation of this tumor suppressor is specific for FTC. In conclusion, LOH at 7q31 is a frequent event in differentiated thyroid cancer, and we have defined a 2 cM SCDR specific for FTC.
我们使用针对人类7号染色体长臂7q31区域的13个微卫星标记，分析了42例分化型甲状腺肿瘤，其中包括15例滤泡性腺瘤（FA）、13例甲状腺乳头状癌（PTC）和14例滤泡状甲状腺癌（FTC）；该区域在其他几种肿瘤类型中也经常发生缺失。总体而言，在分析的42个样本中，有20个（48%）显示出一个或多个检测标记的杂合性缺失（LOH）。LOH在FTC（甲状腺肿瘤中恶性程度最高的类型）中检测最为频繁（78%）。在这种肿瘤类型中定义了一个最小共同缺失区域（SCDR），其两侧为标记D7S480和D7S490。这个SCDR与D7S522不同，D7S522是许多其他肿瘤中最常缺失的位点，仅在一例FTC中发生缺失。D7S522在6例有信息的PTC中有2例显示出LOH。在FTC的SCDR中，没有PTC显示出LOH，只有2例FA显示出LOH。由于FA被认为是FTC的癌前阶段，我们的结果表明，在腺瘤向癌进展过程中，7q31.2处假定的肿瘤抑制基因可能会失活。PTC中该位点不存在LOH表明该肿瘤抑制基因的失活是FTC特有的。总之，7q31处的LOH在分化型甲状腺癌中是一个常见事件，并且我们定义了一个特定于FTC的2 cM SCDR。
