LOSS OF HETEROZYGOSITY FOR THE SHORT ARM OF CHROMOSOME-1 IN HUMAN NEUROBLASTOMAS - CORRELATION WITH N-MYC AMPLIFICATION
LOSS OF HETEROZYGOSITY FOR THE SHORT ARM OF CHROMOSOME-1 IN HUMAN NEUROBLASTOMAS - CORRELATION WITH N-MYC AMPLIFICATION
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DOI：
10.1073/pnas.86.10.3753
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发表时间：
1989-05-01
影响因子：
11.1
通讯作者：
BRODEUR, GM
中科院分区：
文献类型：
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作者：
FONG, CT;DRACOPOLI, NC;BRODEUR, GM
1号染色体短臂的部分单体性是人类神经母细胞瘤中发现的最一致的细胞遗传学异常，但其总体频率和意义尚不清楚。使用一组识别限制性片段长度多态性的 1 号染色体特异性 DNA 探针，我们证明 47 例人类神经母细胞瘤中有 13 例 (28%) 在 1 号染色体远端短臂上的一个或多个位点具有体细胞杂合性丢失 (LOH)。显示 LOH 最一致的染色体区域位于 1p36.1 和 1p36.3 之间；该区域的一个或多个基因的丢失可能对于神经母细胞瘤的发生或进展至关重要。人类神经母细胞瘤中的 LOH 区域可能类似于嗜铬细胞瘤、甲状腺髓样癌和黑色素瘤，这些也是神经嵴起源的肿瘤。尽管远端染色体 1p 的 LOH 可能发生在神经母细胞瘤的早期阶段，但这种缺失通常发生在临床晚期的肿瘤中。 1 号染色体短臂的 LOH 与 N-myc 扩增显着相关，表明这两个遗传事件是相关的。事实上，这两种病变似乎是具有遗传特征的特别具有侵袭性的神经母细胞瘤的一个子集的特征。
Partial monosomy of the short arm of chromosome 1 is the most consistent cytogenetic abnormality found in human neuroblastomas, but its overall frequency and significance are unclear. Using a panel of chromosome-1-specific DNA probes that identify restriction fragment length polymorphisms, we demonstrate that 13 of 47 human neuroblastomas (28%) have somatic loss of heterozygosity (LOH) at one or more loci on the distal short arm of chromosome 1. The chromosomal region that shows LOH most consistently is between 1p36.1 and 1p36.3; loss of a gene or genes in this region may be critical for the development or progression of neuroblastomas. The region of LOH in human neuroblastoma may resemble that described for pheochromocytoma, medullary thyroid carcinoma, and melanoma, which are also tumours of neural-crest origin. Although LOH for distal chromosome 1p can occur in early stages of neuroblastoma, the loss usually occurs in tumors of advanced clinical stages. LOH for the short arm of chromosome 1 correlates significantly with N-myc amplification, suggesting that these two genetic events are related. Indeed, these two lesions appear to characterize a genetically distinct subset of particularly aggressive neuroblastomas.