Molecular Characterization by Array Comparative Genomic Hybridization and DNA Sequencing of 194 Desmoid Tumors
Molecular Characterization by Array Comparative Genomic Hybridization and DNA Sequencing of 194 Desmoid Tumors
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DOI：
10.1002/gcc.20766
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发表时间：
2010-06-01
影响因子：
3.7
通讯作者：
Coindre, Jean-Michel
中科院分区：
文献类型：
--
作者：
Salas, Sebastien;Chibon, Frederic;Coindre, Jean-Michel
硬纤维瘤是成纤维细胞/肌纤维母细胞增殖。此前的研究报告称，84%的人检测到CTNNB1突变，并且在几例缺乏CTNNB1突变的散发性硬纤维瘤病例中发现了APC基因突变。通过比较基因组杂交（CGH）分析了四十个肿瘤。核型和荧光原位杂交揭示了 8 三体性的非随机发生与复发风险增加相关。我们报告了第一个分子特征，包括大量患者。我们对 194 个肿瘤的冷冻样本进行了阵列 CGH，并在没有 CNNTB1 突变的患者中筛查了 APC 突变。观察到基因组正常肿瘤的发生率很高。在 46 个发生染色体变化的肿瘤中，有 40 个肿瘤中发现了四种相关且反复发生的改变（6q 缺失、5q 缺失、20q 增加和 8 号染色体增加）。 8 号和 20 号染色体的增加与复发风险增加无关。 5q 缺失的病例在 5q22.5 中具有最小共同区域，包括 APC 基因座。 APC 的改变（包括整个基因座的丢失）和 CTNNB1 突变可以解释 89% 散发性硬纤维瘤和加德纳综合征背景下发生的硬纤维瘤的肿瘤发生。为了更好地了解硬纤维瘤发生和进展的发病途径，需要研究 8q 和 20q 增益、6q 和 5q 丢失，以及 Wnt/β-连环蛋白途径的研究。 (C) 2010 Wiley-Liss, Inc.
Desmoid tumors are fibroblastic/myofibroblastic proliferations. Previous studies reported that CTNNB1 mutations were detected in 84% and that mutations of the APC gene were found in several cases of sporadic desmoid tumors lacking CTNNB1 mutations. Forty tumors were analyzed by comparative genomic hybridization (CGH). Karyotype and fluorescence in situ hybridization revealed a nonrandom occurrence of trisomy 8 associated with an increased risk of recurrence. We report the first molecular characterization including a large series of patients. We performed array CGH on frozen samples of 194 tumors, and we screened for APC mutations in patients without: CNNTB1 mutation. A high frequency of genomically normal tumors was observed. Four relevant and recurrent alterations (loss of 6q, loss of 5q, gain of 20q, and gain of Chromosome 8) were found in 40 out of 46 tumors with chromosomal changes. Gain of Chromosomes 8 and 20 was not associated with an increased risk of recurrence. Cases with loss of 5q had a minimal common region in 5q22.5 including the APC locus. Alterations of APC, including loss of the entire locus, and CTNNB1 mutation could explain the tumorigenesis in 89% of sporadic desmoids tumors and desmoids tumors occurring in the context of Gardner's syndrome. A better understanding of the pathogenetic pathways in the initiation and progression of desmoid tumors requires studies of 8q and 20q gains, as well as of 6q and 5q losses, and study of the Wnt/beta-catenin pathway. (C) 2010 Wiley-Liss, Inc.