A catalog of genes homozygously deleted in human lung cancer and the candidacy of PTPRD as a tumor suppressor gene.
A catalog of genes homozygously deleted in human lung cancer and the candidacy of PTPRD as a tumor suppressor gene.
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DOI：
10.1002/gcc.20746
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发表时间：
2010-04
影响因子：
3.7
通讯作者：
Yokota, Jun
中科院分区：
文献类型：
--
作者：
Kohno, Takashi;Otsuka, Ayaka;Girard, Luc;Sato, Masanori;Iwakawa, Reika;Ogiwara, Hideaki;Sanchez-Cespedes, Montse;Minna, John D.;Yokota, Jun
对52株肺癌细胞系进行DNA阵列全基因组扫描，并对包括扫描细胞系在内的74株细胞系进行基因组PCR，共鉴定出176个肺癌纯合缺失基因。这些基因的一个或多个外显子在一个（1%）到20个（27%）细胞系中被纯合删除。这些基因包括已知的肿瘤抑制基因，如CDKN2A/p16、RB1和SMAD4，以及在几种人类癌症中报道的半合子或纯合子缺失的候选肿瘤抑制基因，如FHIT、KEAP1和LRP1B/LRP-DIP。位于9p21的CDKN2A/p16和p14ARF最常被删除（20/ 74,27 %）。在定位于9p21以外区域的基因中，PTPRD基因缺失最多（8/ 74,11%）。在8/74（11%）的肺癌细胞系和4/95（4%）的肺癌手术标本中检测到PTPRD基因的体细胞突变，包括无意义突变。PTPRD在大多数肺癌细胞系和手术标本中表达降低（约80%）。因此，PTPRD是肺癌的候选抑癌基因。19种肺癌细胞系的微阵列表达谱也表明，176个基因中的一些，如KANK和ADAMTS1，会被表观遗传改变优先失活。对这176个基因的遗传/表观遗传和功能研究将增加我们对肺癌发生背后的分子机制的理解。
A total of 176 genes homozygously deleted in human lung cancer were identified by DNA array-based whole genome scanning of 52 lung cancer cell lines and subsequent genomic PCR in 74 cell lines, including the 52 cell lines scanned. One or more exons of these genes were homozygously deleted in one (1%) to 20 (27%) cell lines. These genes included known tumor suppressor genes, e.g., CDKN2A/p16, RB1, and SMAD4, and candidate tumor suppressor genes whose hemizygous or homozygous deletions were reported in several types of human cancers, such as FHIT, KEAP1, and LRP1B/LRP-DIP. CDKN2A/p16 and p14ARF located in 9p21 were most frequently deleted (20/74, 27%). The PTPRD gene was most frequently deleted (8/74, 11%) among genes mapping to regions other than 9p21. Somatic mutations, including a nonsense mutation, of the PTPRD gene were detected in 8/74 (11%) of cell lines and 4/95 (4%) of surgical specimens of lung cancer. Reduced PTPRD expression was observed in the majority (>80%) of cell lines and surgical specimens of lung cancer. Therefore, PTPRD is a candidate tumor suppressor gene in lung cancer. Microarray-based expression profiling of 19 lung cancer cell lines also indicated that some of the 176 genes, such as KANK and ADAMTS1, are preferentially inactivated by epigenetic alterations. Genetic/epigenetic as well as functional studies of these 176 genes will increase our understanding of molecular mechanisms behind lung carcinogenesis.
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DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.9
作者：
Medina, Pedro P.;Romero, Octavio A.;Sanchez-Cespedes, Montse
通讯作者：
Sanchez-Cespedes, Montse
影响因子：
11.2
作者：
Imoto, Issei;Izumi, Hiroyuki;Inazawa, Johji
通讯作者：
Inazawa, Johji
影响因子：
3.7
作者：
Nagayama, Kazuhiro;Kohno, Takashi;Yokota, Jun
通讯作者：
Yokota, Jun
影响因子：
11.2
作者：
Ohta, Tsutonm;Iijima, Kumiko;Hirohashi, Setsuo
通讯作者：
Hirohashi, Setsuo