Different patterns of 11q allelic losses in digestive endocrine tumors
Different patterns of 11q allelic losses in digestive endocrine tumors
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DOI：
10.1053/hupa.2002.32219
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发表时间：
2002-03-01
期刊：
影响因子：
3.3
通讯作者：
Bordi, C
中科院分区：
文献类型：
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作者：
D'Adda, T;Pizzi, S;Bordi, C
大多数前肠消化道内分泌肿瘤可能与 I 型多内分泌 (MEN-1) 综合征有关。相反，中肠/后肠类癌从未显示出这种关联。为了研究 MEN-1 基因及其远端假定的其他肿瘤抑制基因的发病机制，对 27 个前肠（胰腺内分泌肿瘤 [PET]）、23 个中肠（回肠和阑尾）和 3 个后肠（直肠）进行了染色体 11q13 至 11qter 杂合性丢失 (LOH) 的比较分析。 内分泌肿瘤。在 23 个散发性和所有 4 个 MEN-1 相关 PET 中，有 52% 观察到 11q13 处 MEN-1 基因位点的 LOH，并且发现一致且连续地跨越 11qter 所研究的最远端标记。相比之下，在回肠（中肠）类癌中仅观察到 11q 标记物的偶尔、不连续且大部分为间质性 LOH，而在所有阑尾（中肠）和直肠（后肠）类癌中未发现 LOH。在散发性 PET 中，LOH 从 MEN-1 区域一致延伸至 11qter，这表明通过染色体断裂和 11q 染色体完全丢失而导致基因失活的机制。此外，这些结果扩展到 11q13 区域之外，寻找可能参与这些肿瘤发生的其他抑癌基因。中肠/后肠类癌中 11q 缺失频率低、延伸有限且分布不连续，表明 MEN-1 基因不参与这些肿瘤的发病机制。版权所有2002，Elsevier Science（美国）。版权所有。
Most foregut digestive endocrine neoplasms may be associated with the multiple endocrine type I (MEN-1) syndrome. In contrast, midgut/hindgut carcinoids never show such association. To investigate the pathogenetic involvement of the MEN-1 gene and of putative additional oncosuppressor gene(s) distal to it, a comparative analysis of loss of heterozygosity (LOH) at chromosome 11q13 to 11qter was performed in 27 foregut (pancreatic endocrine tumors [PETs]), 23 midgut (ileal and appendiceal), and 3 hindgut (rectal) endocrine tumors. LOH at the MEN-1 gene locus at 11q13 was observed in 52% of the 23 sporadic and in all 4 MEN-1-associated PETs and was found to consistently and continuously span to the most distal marker investigated at 11qter. In contrast, only occasional, discontinuous, and mostly interstitial LOH for 11q markers was observed in ileal (midgut) carcinoids, whereas no LOH was found in all appendiceal (midgut) and rectal (hindgut) carcinoids. The consistent extension of LOH from the MEN-1 region to 11qter in sporadic PETs suggests a mechanism of gene inactivation via chromosomal breakage and complete loss of chromosome 11q; furthermore, these results expand beyond the 11q13 region the search for additional oncosuppressor gene(s) potentially involved in the genesis of these neoplasms. The low frequency, limited extension, and discontinuous distribution of 11q deletions in midgut/hindgut carcinoids suggest that MEN-1 gene is not involved in the pathogenesis of these tumors. Copyright 2002, Elsevier Science (USA). All rights reserved.