MICROSATELLITE ALTERATIONS AS CLONAL MARKERS FOR THE DETECTION OF HUMAN CANCER
MICROSATELLITE ALTERATIONS AS CLONAL MARKERS FOR THE DETECTION OF HUMAN CANCER
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DOI：
10.1073/pnas.91.21.9871
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发表时间：
1994-10-11
影响因子：
11.1
通讯作者：
SIDRANSKY, D
中科院分区：
文献类型：
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作者：
MAO, L;LEE, DJ;SIDRANSKY, D
微卫星不稳定性是遗传性非息肉病性结直肠癌（HNPCC）的一个重要特征。最近发现的遗传不稳定性的小细胞肺癌，与HNPCC无关的肿瘤，使我们调查可能存在的微卫星改变在其他肿瘤类型。我们通过聚合酶链反应检测了100例头颈癌、膀胱癌和肺癌患者的正常和肿瘤对DNA中的52个微卫星重复序列。虽然改变是罕见的，在二核苷酸重复，较大的（三或四核苷酸）重复被发现是更多的pi one扩展或删除。我们用一组9个三核苷酸和四核苷酸重复标记筛选了100个肿瘤，并确定了26个（26%）在至少一个位点显示改变。这一观察结果促使我们研究使用微卫星改变作为标记来检测病理样品中克隆性肿瘤衍生细胞群的可能性。在原发性肿瘤中检测到的相同微卫星改变在相应的尿液、痰液和受影响患者的手术切缘中被成功鉴定。这项研究表明，适当选择的微卫星位点通常在许多癌症中发生改变，并可作为其检测的克隆标记。
Microsatellite instability has been reported to be an important feature of tumors from hereditary nonpolyposis colorectal carcinoma (HNPCC) patients. The recent discovery of genetic instability in small cell lung carcinoma, a neoplasm not associated with HNPCC, led us to investigate the possible presence of microsatellite alterations in other tumor types. We examined 52 microsatellite repeat sequences in the DNA of normal and tumor pairs from 100 head and neck, bladder, and lung cancer patients by the polymerase chain reaction. Although alterations were rare in dinucleotide repeats, larger (tri- or tetranucleotide) repeats were found to be more pi one to expansion or deletion. We screened 100 tumors with a panel of nine tri- and tetranucleotide repeat markers and identified 26 (26%) that displayed alterations in at least one locus. This observation prompted us to examine the possibility of using microsatellite alterations as markers to detect clonal tumor-derived cell populations in pathologic samples. The identical microsatellite alterations detected in the primary tumors were successfully identified in corresponding urine, sputum, and surgical margins from affected patients. This study demonstrates that appropriately selected microsatellite loci are commonly altered in many cancers and can serve as clonal markers for their detection.