Microarray-based CGH of sporadic and syndrome-related pheochromocytomas using a 0.1-0.2 Mb bacterial artificial chromosome array spanning chromosome arm 1p
Microarray-based CGH of sporadic and syndrome-related pheochromocytomas using a 0.1-0.2 Mb bacterial artificial chromosome array spanning chromosome arm 1p
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DOI：
10.1002/gcc.20268
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发表时间：
2006-01-01
影响因子：
3.7
通讯作者：
de Krijger, RR
中科院分区：
文献类型：
--
作者：
Aarts, M;Dannenberg, H;de Krijger, RR
嗜铬细胞瘤是一种少见的神经内分泌肿瘤，主要发生于肾上腺髓质。它们偶尔出现或继发于遗传性癌症综合征，如多发性内分泌肿瘤II型（MEN 2），von Hippel-Lindau病（VHL）或神经纤维瘤病1型（NFI）。1 p缺失是最常见的遗传变异，尤其是在MEN 2相关和散发性PCC中。以前的研究揭示了三个区域的共同体细胞损失的染色体臂I p，使用基于染色体的比较基因组杂交（CGH）和洛分析。为了以更高的分辨率和灵敏度研究这些染色体畸变，我们对13例散发性和II综合征相关（10例MEN 2A相关和1例NFI相关）肿瘤进行了基于微阵列的CGH。该阵列由642个重叠的细菌人工染色体（BAC）克隆组成，定位于1p11.2-p36.33。24例中18例（75%）检测到1 p染色体缺失。在9例1 p部分缺失的肿瘤中，6例（25%）缺失区域仅限于1cen-1p32.3，表明存在遗传不稳定区域。本研究中缺失的共有区域涉及1cen-1p21.1、1p21.3-1p.31.3和1p34.3-1p36.33。总之，这些数据有力地表明，染色体臂I p是多个肿瘤抑制基因的位点，尽管潜在的候选基因CDKN 2C和PTPRF/LAR不包括在这些区域中。(c)2005 Wiley-Liss，Inc.
Pheochromocytomas (PCC) are relatively rare neuroendocrine tumors, mainly of the adrenal medulla. They arise sporadically or occur secondary to inherited cancer syndromes, such as multiple endocrine neoplasia type II (MEN2), von Hippel-Lindau disease (VHL), or neurofibromatosis type 1 (NFI). Loss of 1p is the most frequently encountered genetic alteration, especially in MEN2-related and sporadic PCC. Previous studies have revealed three regions of common somatic loss on chromosome arm I p, using chromosome-based comparative genomic hybridization (CGH) and LOH analysis. To investigate these chromosomal aberrations with a higher resolution and sensitivity, we performed microarray-based CGH with 13 sporadic and I I syndrome-related (10 MEN2A-related and 1 NFI-related) tumors. The array consisted of 642 overlapping bacterial artificial chromosome (BAC) clones mapped to 1p1 1.2-p36.33. Chromosomal deletions on 1p were detected in 18 of 24 cases (75%). Among 9 tumors with partial 1p loss, the deleted region was restricted to 1cen-1p32.3 in six cases (25%), indicating a region of genetic instability. The consensus regions of deletion in this study involved 1cen-1p21.1, 1p21.3-1p.31.3, and 1p34.3-1p36.33. In conclusion, these data strongly suggest that chromosome arm I p is the site for multiple tumor suppressor genes, although the potential candidate genes CDKN2C and PTPRF/LAR are not included in these regions. (c) 2005 Wiley-Liss, Inc.