Evidence for a novel tumor suppressor gene on chromosome 15 associated with progression to a metastatic stage in breast cancer.
Evidence for a novel tumor suppressor gene on chromosome 15 associated with progression to a metastatic stage in breast cancer.
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发表时间：
1996-03
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影响因子：
8
通讯作者：
W. Wick;I. Petersen;R. Schmutzler;B. Wolfarth;D. Lenartz;E. Bierhoff;Jörg Hümmerich;Daniel J. Müller;A. Stangl;J. Schramm;Otmar D. Wiestler;A. Deimling
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作者：
W. Wick;I. Petersen;R. Schmutzler;B. Wolfarth;D. Lenartz;E. Bierhoff;Jörg Hümmerich;Daniel J. Müller;A. Stangl;J. Schramm;Otmar D. Wiestler;A. Deimling
杂合性缺失（洛）研究已成为一个有价值的指标，肿瘤抑制基因参与的形成或发展的癌症。我们在这里提出的数据表明，人类染色体15窝藏一个新的推定的肿瘤抑制基因，似乎发挥了作用，在晚期阶段的癌变，这可能与乳腺癌的转移。本研究用15号染色体上的13个多态性微卫星标记分析了101例患者的153例原发癌和转移癌的洛缺失。肿瘤包括肺癌49例，乳腺癌29例，结直肠癌9例，肾癌5例，胰腺癌5例，膀胱癌2例，前列腺癌和卵巢癌各1例。在42/99例（42%）有信息的患者中观察到LOH 15。在转移性肿瘤中，在37/68（54%）中观察到LOH 15。在肺癌（56%）、乳腺癌（70%）和结直肠癌（67%）的转移灶中检测到等位基因丢失的高发生率。在乳腺癌中，LOH 15在非转移性肿瘤（11%）和脑转移性肿瘤（70%）中的频率差异有显著性（P<0.01）。在染色体臂17 p上没有观察到这种差异，而在非转移性乳腺肿瘤（73%）和乳腺癌转移（90%）中产生高比例的洛缺失。在16例患者中，可以检测到间质缺失。共同的重叠区域从D15 S231延伸到D15 S641，从而将该推定的肿瘤抑制基因定位到染色体15 q14。我们的数据表明，15号染色体上的基因有助于转移癌的发病机制。
Loss of heterozygosity (LOH) studies have emerged as a valuable indicator for tumor suppressor genes involved in the formation or progression of carcinomas. We here present data indicating that human chromosome 15 harbours a novel putative tumor suppressor gene which appears to play a role during later stages of carcinogenesis and which may be associated with metastasis in breast cancer. In this study, 153 primary and metastatic carcinomas from 101 patients have been analysed for LOH with 13 polymorphic microsatellite markers on chromosome 15. The tumors included carcinoma of the lung in 49 patients, breast carcinoma in 29, colorectal carcinoma in nine, renal carcinoma in five, pancreatic carcinoma in five, urinary bladder carcinoma in two and prostate carcinoma and ovarial carcinoma in one patient each. LOH15 was seen in 42/99 (42%) informative patients. In metastatic tumors, LOH15 was observed in 37/68 (54%). High incidences of allelic losses were detected in metastases from lung (56%), breast (70%) and colorectal (67%) carcinomas. In carcinomas of the breast, there was a significant difference (P<0.01) in LOH15 frequencies between non-metastatic tumors (11%) and brain metastases (70%). Such a difference was not observed on the chromosomal arm 17p which yielded high proportions of LOH in both non metastatic breast tumor (73%) and breast carcinoma metastases (90%). In 16 patients, interstitial deletions could be detected. The common region of overlap extended from D15S231 to D15S641, thus mapping this putative tumor suppressor gene to chromosome 15q14. Our data indicate that a gene on chromosome 15 contributes to the pathogenesis of metastatic carcinoma.