Frequent loss xq25 on the inactive X chromosome in primary breast carcinomas is associated with tumor grade and axillary lymph node metastasis
Frequent loss xq25 on the inactive X chromosome in primary breast carcinomas is associated with tumor grade and axillary lymph node metastasis
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DOI：
10.1002/gcc.10024
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发表时间：
2002-03-01
影响因子：
3.7
通讯作者：
Malkhosyan, SR
中科院分区：
文献类型：
--
作者：
Piao, Z;Malkhosyan, SR
我们先前应用任意启动的聚合酶链式反应DNA指纹图谱来鉴定原发性乳腺癌的分子遗传改变。最常见的指纹改变之一是32%的肿瘤的MCGI-B2带强度降低，表明X染色体片段反复丢失。本文报道了这些染色体缺失的图谱分析。MCGI-B2的亚染色体起源为Xq25染色体区域。对72例浸润性导管癌进行了杂合性缺失(LOH)分析，共检测了7个跨越Xq25的微卫星标记。X染色体缺失的最小共同区域位于标记DXS8059和DXS8009之间，DXS8098基因座的LOH频率最高，为52.4%。DXS8098的LOH与较大的肿瘤大小(P=0.048，Fisher精确检验)、较高的组织学分级(P=0.036，Fisher精确检验)和腋窝淋巴结转移(P=0.020，Fisher精确检验)相关。这些结果表明，Xq25区域含有一个可能的肿瘤抑制基因，该基因在乳腺癌中的失活与肿瘤的进展和转移有关。因此，该区域的LOH有可能被用作疾病发展的预后标记物。在女性身上，两条X染色体中有一条在转录上是沉默的。在本研究中检测到的Xq25区域的丢失优先发生在不活跃的X染色体上。这表明推测的肿瘤抑制基因可能逃脱了X的失活。(C)2002年Wiley-Liss，Inc.
We previously applied arbitrarily primed polymerase chain reaction DNA fingerprinting to identify molecular genetic alterations in primary breast carcinomas. One of the most frequently observed fingerprint alterations was a reduction in the intensity of the MCGI-B2 band in 32% of tumors, indicating recurrent loss of X-chromosome segments. This article reports a mapping analysis of those chromosomal deletions. The subchromosomal origin of MCGI-B2 was determined to be the Xq25 chromosomal region. Loss of heterozygosity (LOH) analysis was carried out on 72 infiltrating ductal carcinomas with a panel of seven microsatellite markers spanning Xq25. The smallest common region of the X-chromosome deletions was mapped to between markers DXS8059 and DXS8009, with the highest LOH frequency of 52.4% at the DXS8098 locus. The LOH at DXS8098 was associated with larger tumor size (> 3 cm) (P = 0.048, Fisher exact test), higher histologic grade (P = 0.036, Fisher exact test), and axillary lymph node metastasis (P = 0.020, Fisher exact test). These results suggest that the Xq25 region harbors a putative tumor suppressor gene whose inactivation in breast cancer is associated with tumor progression and metastasis. LOH at this region, therefore, potentially could be used as a prognostic marker for disease development. One of the two X chromosomes is transcriptionally silent in women. The loss of the Xq25 region detected in this study occurred preferentially on the inactive X chromosome. This suggests that the putative tumor suppressor gene may escape X inactivation. (C) 2002 Wiley-Liss, Inc.