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17号染色体短臂端粒的高度缺失表明肿瘤抑制基因位置临近。

High levels of loss at the 17p telomere suggest the close proximity of a tumour suppressor.

作者信息

White G R, Stack M, Santibáñez-Koref M, Liscia D S, Venesio T, Wang J C, Helms C, Donis-Keller H, Betticher D C, Altermatt H J, Hoban P R, Heighway J

机构信息

CRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.

出版信息

Br J Cancer. 1996 Sep;74(6):863-70. doi: 10.1038/bjc.1996.449.

DOI:10.1038/bjc.1996.449
PMID:8826850
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2074733/
Abstract

High levels of loss of distal markers on 17p13.3 in breast cancer suggested the presence within the region of at least one tumour-suppressor gene. Here we describe the derivation of two biallelic polymorphisms from the 17p telomeric yeast artificial chromosome (YAC) TYAC98. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR analysis demonstrated that the high level of allelic imbalance observed in breast tumours represented loss of constitutional heterozygosity (LOH) and that this LOH extended to the telomere. Lung carcinoma (but not Wilms' tumour)-derived DNA again revealed a high level of loss of subtelomeric 17p sequences. Telomeric microsatellite polymorphisms from other chromosome arms did not show such elevated loss in either tumour type. This suggested that the 17p loss observed did not reflect a general telomeric instability and provided further evidence for the presence of a breast cancer tumour-suppressor gene in the distal region of 17p13.3.

摘要

乳腺癌中17p13.3上远端标记的高度缺失表明该区域内至少存在一个肿瘤抑制基因。在此，我们描述了从17p端粒酵母人工染色体（YAC）TYAC98衍生出的两个双等位基因多态性。聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和多重PCR分析表明，在乳腺肿瘤中观察到的高度等位基因不平衡代表了组成型杂合性缺失（LOH），并且这种LOH延伸至端粒。肺癌（但不是肾母细胞瘤）来源的DNA再次显示出亚端粒17p序列的高度缺失。来自其他染色体臂的端粒微卫星多态性在这两种肿瘤类型中均未显示出如此高的缺失率。这表明观察到的17p缺失并不反映一般的端粒不稳定性，并为17p13.3远端区域存在乳腺癌肿瘤抑制基因提供了进一步的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7234/2074733/a320d7970231/brjcancer00022-0035-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7234/2074733/a62ee01208d2/brjcancer00022-0034-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7234/2074733/c9824de11c80/brjcancer00022-0034-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7234/2074733/a320d7970231/brjcancer00022-0035-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7234/2074733/a62ee01208d2/brjcancer00022-0034-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7234/2074733/c9824de11c80/brjcancer00022-0034-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7234/2074733/a320d7970231/brjcancer00022-0035-a.jpg

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本文引用的文献

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Index, comprehensive microsatellite, and unified linkage maps of human chromosome 14 with cytogenetic tie points and a telomere microsatellite marker.人类14号染色体的索引、综合微卫星和统一连锁图谱，带有细胞遗传学连接点和一个端粒微卫星标记。
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乳腺癌杂合性缺失的汇总分析：基因组扫描为多种肿瘤抑制基因提供了比较证据并确定了新的候选区域。
Am J Hum Genet. 2003 Oct;73(4):748-67. doi: 10.1086/378522. Epub 2003 Sep 16.
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Three new regions on chromosome 17p13.3 distal to p53 with possible tumor suppressor gene involvement in lung cancer.17号染色体p13.3上位于p53远端的三个新区域，可能有肿瘤抑制基因参与肺癌的发生。
Jpn J Cancer Res. 2000 Jun;91(6):589-96. doi: 10.1111/j.1349-7006.2000.tb00986.x.
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Prognostic significance of loss of heterozygosity at loci on chromosome 17p13.3-ter in sporadic breast cancer is evidence for a putative tumour suppressor gene.17号染色体17p13.3-末端位点杂合性缺失在散发性乳腺癌中的预后意义是一个假定肿瘤抑制基因存在的证据。
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