Kim Do Ha, Nagano Yasuhiko, Choi In-Seon, White Jill A, Yao James C, Rashid Asif
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Genes Chromosomes Cancer. 2008 Jan;47(1):84-92. doi: 10.1002/gcc.20510.
Well-differentiated neuroendocrine tumors (WDNT, carcinoid tumors) are uncommon indolent neoplasms. The genetic alterations of these tumors are not well characterized. We used genome-wide high-density single nucleotide polymorphism (SNP) array analysis to detect copy number alterations in 29 WDNTs, including seven lung, seven nonileal gastrointestinal, and 15 ileal tumors, and compared with allelic imbalances in 15 pancreatic endocrine tumors (PETs). Most frequent allelic imbalances in WDNTs were losses of chromosome 18 in 10 tumors (34%), chromosome 21 or 21q in six (21%), chromosome 13 or 13q in five (17%) and chromosome 16 or 16q in four (14%) tumors, and amplification of chromosome 20 or 20p in seven (24%) tumors. We also found one tumor with loss of heterozygosity of chromosomes 10 and 15 without copy number loss. These allelic imbalances were associated with primary site of tumor: loss of chromosome 18 was present exclusively in ileal WDNTs (P = 0.001), and loss of chromosome 21 or 21q was more frequent in nonileal gastrointestinal WDNTs (P = 0.02). The tumors with loss of chromosome 21 were larger compared to tumors without loss (P = 0.03). Chromosomal aberrations were less common in WDNTs from lung and gastrointestinal tract compared to PETs (P = 0.001). Our study shows that genome-wide allelotyping using SNP array is a powerful new tool for the analysis of allelic imbalances in WDNTs, and some of these alterations are tumor site-dependent and are different than in PETs.
高分化神经内分泌肿瘤(WDNT,类癌肿瘤)是罕见的惰性肿瘤。这些肿瘤的基因改变尚未得到充分表征。我们使用全基因组高密度单核苷酸多态性(SNP)阵列分析来检测29例WDNT中的拷贝数改变,包括7例肺肿瘤、7例非回肠胃肠道肿瘤和15例回肠肿瘤,并与15例胰腺内分泌肿瘤(PET)中的等位基因失衡进行比较。WDNT中最常见的等位基因失衡是10例肿瘤(34%)中18号染色体缺失,6例(21%)中21号或21q染色体缺失,5例(17%)中13号或13q染色体缺失,4例(14%)肿瘤中16号或16q染色体缺失,7例(24%)肿瘤中20号或20p染色体扩增。我们还发现1例肿瘤存在10号和15号染色体杂合性缺失但无拷贝数丢失。这些等位基因失衡与肿瘤的原发部位相关:18号染色体缺失仅存在于回肠WDNT中(P = 0.001),21号或21q染色体缺失在非回肠胃肠道WDNT中更常见(P = 0.02)。与无21号染色体缺失的肿瘤相比,有21号染色体缺失的肿瘤更大(P = 0.03)。与PET相比,WDNT来自肺和胃肠道的染色体畸变较少见(P = 0.001)。我们的研究表明,使用SNP阵列进行全基因组等位基因分型是分析WDNT中等位基因失衡的一种强大新工具,其中一些改变与肿瘤部位有关,且与PET不同。