Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p.

Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p.
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小细胞肺癌的特征是染色体3p,4q,5q,10q,10q,13q和17p的缺失发生率很高。

DOI:
10.1038/bjc.1997.13
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发表时间:
1997
影响因子:
8.8
通讯作者:
Dietel, M
Dietel, M
中科院分区:
医学1区
文献类型:
--
作者:
Petersen, I;Langreck, H;Wolf, G;Schwendel, A;Psille, R;Vogt, P;Reichel, M B;Ried, T;Dietel, M

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定义小细胞肺癌(SCLC)恶性行为的遗传机制知之甚少。我们对22例尸检SCLC进行了比较基因组杂交(CGH),以筛选肿瘤基因组的基因组失衡。染色体3p的DNA丢失是发生在所有肿瘤中的基本改变。此外,在94%的肿瘤中在染色体10 q上观察到缺失,在86%的肿瘤中在染色体4q、5q、13 q和17 p上观察到缺失。通过染色体3p、5q和10q的杂合性丢失(洛)分析证实DNA丢失。在12例病例中发现了这六种最丰富的遗传变化的同时突变。一个肿瘤携带至少五个缺失。在15号染色体(55%)和16号染色体(45%)上观察到的DNA表达不足较少。22个肿瘤与CGH超核图的叠加清楚地表明了普遍存在的不平衡。在我们看来,染色体丢失的高发生率表明SCLC是由缺失模式定义的,并且多个生长抑制途径的失活特别有助于该类型肿瘤的侵袭性表型。
The genetic mechanisms that define the malignant behaviour of small-cell lung cancer (SCLC) are poorly understood. We performed comparative genomic hybridization (CGH) on 22 autoptic SCLCs to screen the tumour genome for genomic imbalances. DNA loss of chromosome 3p was a basic alteration that occurred in all tumours. Additionally, deletions were observed on chromosome 10q in 94% of tumours and on chromosomes 4q, 5q, 13q and 17p in 86% of tumours. DNA loss was confirmed by loss of heterozygosity (LOH) analysis for chromosomes 3p, 5q and 10q. Simultaneous mutations of these six most abundant genetic changes were found in 12 cases. One single tumour carried at least five deletions. DNA under-representations were observed less frequently on chromosome 15q (55%) and chromosome 16q (45%). The prevalent imbalances were clearly indicated by the superposition of the 22 tumours to a CGH superkaryogram. In our view, the high incidence of chromosomal loss is an indication that SCLC is defined by a pattern of deletions and that the inactivation of multiple growth-inhibitory pathways contributes in particular to the aggressive phenotype of that type of tumour.