Wreesmann Volkert B, Ghossein Ronald A, Patel Snehal G, Harris Charles P, Schnaser Erik A, Shaha Ashok R, Tuttle R Michael, Shah Jatin P, Rao Pulivarthi H, Singh Bhuvanesh
Laboratory of Epithelial Cancer Biology, Head and Neck Service, New York, New York 10021, USA.
Am J Pathol. 2002 Nov;161(5):1549-56. doi: 10.1016/S0002-9440(10)64433-1.
Several lines of evidence suggest that follicular cell-derived thyroid cancers represent a continuum of disease that progresses from the highly curable well-differentiated thyroid cancers to the universally fatal anaplastic cancers. However, the genetic mechanisms underlying thyroid cancer progression remain ill defined. We compared the molecular-cytogenetic profiles derived from comparative genomic hybridization (CGH) analysis of major histological variants of thyroid cancer to define genetic variables associated with progression. Overall, a sequential increase in chromosomal complexity was observed from well-differentiated papillary thyroid cancer to poorly differentiated and anaplastic carcinomas, both in terms of the presence of CGH detectable abnormalities (P = 0.003) and the median number of abnormalities per case (P < 0.001). The presence of multiple abnormalities common to all thyroid cancer variants, including gains of 5p15, 5q11-13, 19p, and 19q and loss of 8p, suggests that these tumors are derived from a common genetic pathway. Gains of 1p34-36, 6p21, 9q34, 17q25, and 20q and losses of 1p11-p31, 2q32-33, 4q11-13, 6q21, and 13q21-31 may represent secondary events in progression, as they were only detected in poorly differentiated and anaplastic carcinomas. Finally, recurrent gains at 3p13-14 and 11q13, and loss of 5q11-31 were unique to anaplastic carcinomas, suggesting they may be markers for anaplastic transformation. Our data suggests that the development of chromosomal instability underlies the progression to more aggressive phenotypes of thyroid cancer and sheds light on the possible genomic aberrations that may be selected for during this process.
多项证据表明，滤泡细胞源性甲状腺癌代表了一种疾病连续体，从高度可治愈的高分化甲状腺癌发展到普遍致命的间变性癌。然而，甲状腺癌进展的遗传机制仍不清楚。我们比较了甲状腺癌主要组织学变体的比较基因组杂交（CGH）分析得出的分子细胞遗传学图谱，以确定与进展相关的遗传变量。总体而言，从高分化乳头状甲状腺癌到低分化和间变性癌，在CGH可检测到的异常存在方面（P = 0.003）以及每例异常的中位数方面（P < 0.001），均观察到染色体复杂性的连续增加。所有甲状腺癌变体共有的多种异常的存在，包括5p15、5q11 - 13、19p和19q的获得以及8p的缺失，表明这些肿瘤源自共同的遗传途径。1p34 - 36、6p21、9q34、17q25和20q的获得以及1p11 - p31、2q32 - 33、4q11 - 13、6q21和13q21 - 31的缺失可能代表进展中的继发事件，因为它们仅在低分化和间变性癌中检测到。最后，3p13 - 14和11q13的反复获得以及5q11 - 31的缺失是间变性癌所特有的，表明它们可能是间变性转化的标志物。我们的数据表明，染色体不稳定性的发展是甲状腺癌向更具侵袭性表型进展的基础，并揭示了在此过程中可能被选择的潜在基因组畸变。
