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散发性人类乳腺癌中的杂合性缺失:11q22与11q23.3之间的一个共同区域

Loss of heterozygosity in sporadic human breast carcinoma: a common region between 11q22 and 11q23.3.

作者信息

Hampton G M, Mannermaa A, Winqvist R, Alavaikko M, Blanco G, Taskinen P J, Kiviniemi H, Newsham I, Cavenee W K, Evans G A

机构信息

Molecular Genetics Laboratory, Salk Institute for Biological Studies, La Jolla, California 92318-5800.

出版信息

Cancer Res. 1994 Sep 1;54(17):4586-9.

PMID:8062246
Abstract

The development of sporadic human breast cancer is associated with the accumulation of genetic alterations on several chromosomes. In the case of chromosome 11, loss of heterozygosity (LOH) at loci on the short arm has been well documented and suggests the presence of a suppressor gene(s) at 11p15.5. However, the evidence for similar events on the long arm is less compelling. Here, we determined the prevalence of LOH for chromosome 11q in 44 malignant and 3 benign cases of unselected sporadic breast tumor samples. We found that alteration of chromosome 11q is common in the pathogenesis of breast cancer as 19 of 44 (43%) malignant tumor specimens exhibited LOH. Eleven (58%) of these genetic alterations were specific to the long arm of the chromosome. The smallest region of shared LOH places the target between 11q22 and 11q23.3, the same general region frequently altered in cancers of the ovary, colon, skin, and uterine cervix, perhaps indicating the location of a tumor suppressor gene or genes of importance in each of these different tumor types.

摘要

散发性人类乳腺癌的发生与多条染色体上基因改变的累积有关。就11号染色体而言,短臂上基因座的杂合性缺失(LOH)已有充分记录,提示在11p15.5存在一个或多个抑癌基因。然而,关于长臂上类似事件的证据则不那么确凿。在此,我们测定了44例未经选择的散发性乳腺肿瘤样本(其中44例为恶性,3例为良性)中11号染色体长臂(11q)的LOH发生率。我们发现,11q染色体改变在乳腺癌发病机制中很常见,因为44例恶性肿瘤标本中有19例(43%)出现了LOH。其中11例(58%)基因改变特异性发生在染色体长臂。共享LOH的最小区域将目标定位在11q22和11q23.3之间,这一区域在卵巢癌、结肠癌、皮肤癌和宫颈癌中也经常发生改变,这或许表明该区域存在一个或多个在这些不同肿瘤类型中都很重要的抑癌基因。

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