MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines.
MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines.
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DOI：
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发表时间：
1997-12
期刊：
影响因子：
11.2
通讯作者：
D. Teng;Rong Hu;Huai-En Lin;T. Davis;D. Iliev;C. Frye;B. Swedlund;Kipp L. Hansen;V. L. Vinson-V.
中科院分区：
文献类型：
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作者：
D. Teng;Rong Hu;Huai-En Lin;T. Davis;D. Iliev;C. Frye;B. Swedlund;Kipp L. Hansen;V. L. Vinson-V.
MMAC 1/PTEN是一个位于人类染色体10 q23区的候选抑癌基因，最近在几种胶质瘤、乳腺癌、前列腺癌和肾癌标本或细胞系中观察到的序列改变的基础上被鉴定出来。为了进一步研究该基因在人类癌症中的突变谱，我们检测了大量人类肿瘤标本和多种类型的癌细胞系的10 q23等位基因丢失和MMAC 1序列改变。在MMAC 1基因座的杂合性丢失（洛）中观察到约一半的样本检查，与许多癌症的10 q等位基因丢失报告的高频率一致。迄今为止，在124例表现出洛缺失的肿瘤标本中，我们已经筛查了MMAC 1的改变，我们在13例（约10%）原发性肿瘤中检测到了变异体;在胶质母细胞瘤标本中发现了最高频率的变异体（约23%）。在该基因中发现的新变异包括黑色素瘤样本中的错义变异和儿童胶质母细胞瘤中的剪接变异和无义突变。在76个针对可能的洛杂合性缺失进行预筛选的肿瘤细胞系中，有12个（约16%）细胞系检测到了MMAC 1的微序列改变，包括来自星形细胞瘤、白血病和黑色素瘤肿瘤以及膀胱癌、乳腺癌、肺癌、前列腺癌、颌下腺癌和睾丸癌的细胞系。此外，在这组肿瘤细胞系中，我们检测到11个（约14%）纯合缺失，消除了MMAC 1的编码部分，这是我们的方法在原发性肿瘤中未检测到的一类异常。这些数据支持在多种人类癌症类型中发生失活MMAC 1改变。此外，我们报告的MMAC 1定位在9号染色体上的一个假定的假基因的发现。
A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (approximately 10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (approximately 23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (approximately 16%) of the lines, including those derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (approximately 14%) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.