Hemmer S, Wasenius V M, Knuutila S, Franssila K, Joensuu H
Departments of Oncology and Pathology and the Laboratory of Medical Genetics, Helsinki University Central Hospital, Helsinki, Finland.
Am J Pathol. 1999 May;154(5):1539-47. doi: 10.1016/S0002-9440(10)65407-7.
The genetic changes leading to thyroid cancer are poorly characterized. We studied DNA copy number changes by comparative genomic hybridization (CGH) in 69 primary thyroid carcinomas. In papillary carcinoma, DNA copy number changes were rare (3 of 26, 12%). The changes were all gains, and they were associated with old age (P = 0.01) and the presence of cervical lymph node metastases at presentation (P = 0.08). DNA copy number changes were much more frequent in follicular carcinoma (16 of 20, 80%) than in papillary carcinoma (P < 0.0001), and follicular carcinomas had more often deletions (13/20 versus 0/26, P < 0.0001). Loss of chromosome 22 was common in follicular carcinoma (n = 7, 35%), it was more often seen in widely invasive than in minimally invasive follicular carcinoma (54% versus 0%, P = 0.04), and it was associated with old age at presentation (P = 0.01). In three of the four patients with follicular carcinoma who died of cancer, the tumor had loss of chromosome 22. DNA copy number changes were found in 5 (50%) of the 10 medullary carcinomas studied. Four of these five carcinomas had deletions, and in two of them there was deletion of chromosome 22. Eleven (85%) of the thirteen anaplastic carcinomas investigated had DNA copy number changes, of which five had deletions, and one had deletion of chromosome 22. The most common gains in anaplastic carcinoma were in chromosomes 7p (p22-pter, 31%), 8q (q22-qter, 23%), and 9q (q34-qter, 23%). We conclude that DNA copy number changes are frequent in follicular, medullary, and anaplastic thyroid carcinoma but rare in papillary carcinoma when studied by CGH. Loss of chromosome 22 is particularly common in follicular carcinoma, and it is associated with the widely invasive type.
导致甲状腺癌的基因变化特征尚不明确。我们通过比较基因组杂交（CGH）研究了69例原发性甲状腺癌的DNA拷贝数变化。在乳头状癌中，DNA拷贝数变化很少见（26例中有3例，占12%）。这些变化均为增益，且与老年（P = 0.01）以及就诊时存在颈部淋巴结转移相关（P = 0.08）。滤泡状癌中DNA拷贝数变化（20例中有16例，占80%）比乳头状癌更为常见（P < 0.0001），并且滤泡状癌更常出现缺失（13/20对比0/26，P < 0.0001）。22号染色体缺失在滤泡状癌中很常见（n = 7，占35%），在广泛浸润性滤泡状癌中比在微小浸润性滤泡状癌中更常出现（54%对比0%，P = 0.04），且与就诊时的老年相关（P = 0.01）。在4例死于癌症的滤泡状癌患者中，有3例肿瘤出现了22号染色体缺失。在所研究的10例髓样癌中，有5例（50%）发现了DNA拷贝数变化。这5例癌中有4例出现缺失，其中2例存在22号染色体缺失。在13例间变性癌中，有11例（85%）存在DNA拷贝数变化，其中5例有缺失，1例存在22号染色体缺失。间变性癌中最常见的增益出现在7号染色体p臂（p22 - pter，占31%）、8号染色体q臂（q22 - qter，占23%）和9号染色体q臂（q34 - qter，占23%）。我们得出结论，通过CGH研究发现，DNA拷贝数变化在滤泡状、髓样和间变性甲状腺癌中很常见，但在乳头状癌中很少见。22号染色体缺失在滤泡状癌中尤为常见，且与广泛浸润型相关。
