Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer onco- and suppressor gene changes.
Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer onco- and suppressor gene changes.
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DOI：
10.1186/1471-2407-13-8
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发表时间：
2013-01-05
期刊：
影响因子：
3.8
通讯作者：
Ishikawa Y
中科院分区：
文献类型：
--
作者：
Ninomiya H;Kato M;Sanada M;Takeuchi K;Inamura K;Motoi N;Nagano H;Nomura K;Sakao Y;Okumura S;Mano H;Ogawa S;Ishikawa Y
一组携带EML4-ALK融合基因的肺腺癌已成为特定治疗的靶点。EML4-ALK融合具有特征性的组织学特征，在从不或轻度吸烟者和年轻患者中更常被检测到。为了深入了解病因学和致癌机制，我们使用单核苷酸多态(SNP)阵列对35个ALK融合阳性和95个阴性的肿瘤进行了等位基因分析，并特别设计了能够进行精确全球基因组图谱分析的软件。ALK融合组和非ALK融合组的染色体总畸变数(得/失)分别为8.42和9.56，虽然得/失模式不同，但差异无统计学意义。有趣的是，在选定的基因组区域中，与癌基因相关的例子如1p34.3(MYCL1)、7q11.2(EGFR)、7p21.1、8q24.21(MYC)、16p13.3、17q12(ERBB2)和17q25.1的增益明显较小。此外，在ALK融合的肿瘤中，9p21.3(CDKN2A)、9p23-24.1(PTPRD)、13q14.2(RB1)等抑癌基因相关区域的变化也明显较少。与SNP阵列的全球基因组比较显示，ALK融合的肿瘤癌基因和抑制基因的变化较少，尽管总体畸变率相似，这表明通过基因融合激活ALK的致癌潜力非常强。
A subset of lung adenocarcinomas harboring an EML4-ALK fusion gene resulting in dominant oncogenic activity has emerged as a target for specific therapy. EML4-ALK fusion confers a characteristic histology and is detected more frequently in never or light smokers and younger patients. To gain insights into etiology and carcinogenic mechanisms we conducted analyses to compare allelotypes of 35 ALK fusion-positive and 95 -negative tumours using single nucleotide polymorphism (SNP) arrays and especially designed software which enabled precise global genomic profiling. Overall aberration numbers (gains + losses) of chromosomal alterations were 8.42 and 9.56 in tumours with and without ALK fusion, respectively, the difference not being statistically significant, although patterns of gain and loss were distinct. Interestingly, among selected genomic regions, oncogene-related examples such as 1p34.3(MYCL1), 7q11.2(EGFR), 7p21.1, 8q24.21(MYC), 16p13.3, 17q12(ERBB2) and 17q25.1 showed significantly less gain. Also, changes in tumour suppressor gene-related regions, such as 9p21.3 (CDKN2A) 9p23-24.1 (PTPRD), 13q14.2 (RB1), were significantly fewer in tumours with ALK fusion. Global genomic comparison with SNP arrays showed tumours with ALK fusion to have fewer alterations in oncogenes and suppressor genes despite a similar overall aberration frequency, suggesting very strong oncogenic potency of ALK activation by gene fusion.
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影响因子：
30.8
作者：
McKay, James D.;Hung, Rayjean J.;Gaborieau, Valerie;Boffetta, Paolo;Chabrier, Amelie;Byrnes, Graham;Zaridze, David;Mukeria, Anush;Szeszenia-Dabrowska, Neonilia;Lissowska, Jolanta;Rudnai, Peter;Fabianova, Eleonora;Mates, Dana;Bencko, Vladimir;Foretova, Lenka;Janout, Vladimir;McLaughlin, John;Shepherd, Frances;Montpetit, Alexandre;Narod, Steven;Krokan, Hans E.;Skorpen, Frank;Elvestad, Maiken Bratt;Vatten, Lars;Njolstad, Inger;Axelsson, Tomas;Chen, Chu;Goodman, Gary;Barnett, Matt;Loomis, Melissa M.;Lubinski, Jan;Matyjasik, Joanna;Lener, Marcin;Oszutowska, Dorota;Field, John;Liloglou, Triantafillos;Xinarianos, George;Cassidy, Adrian;Zelenika, Diana;Boland, Anne;Delepine, Marc;Foglio, Mario;Lechner, Doris;Matsuda, Fumihiko;Blanche, Helene;Gut, Ivo;Heath, Simon;Lathrop, Mark;Brennan, Paul
通讯作者：
Brennan, Paul
EGFR和KRAS突变的NSCLC之间的基因组广泛的SNP比较分析以及非小细胞肺癌中的两种致癌合作模型的表征。
影响因子：
2.7
作者：
Blons, Helene;Pallier, Karine;Le Corre, Delphine;Danel, Claire;Tremblay-Gravel, Maxime;Houdayer, Claude;Fabre-Guillevin, Elizabeth;Riquet, Marc;Dessen, Philippe;Laurent-Puig, Pierre
通讯作者：
Laurent-Puig, Pierre
影响因子：
11.2
作者：
Le Calvez, F;Mukeria, A;Hainaut, P
通讯作者：
Hainaut, P
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Lo, Ken C.;Stein, Leighton C.;Hawthorn, Lesleyann
通讯作者：
Hawthorn, Lesleyann