Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization-positive nonsmall cell lung cancer.
Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization-positive nonsmall cell lung cancer.
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DOI：
10.1002/cncr.27411
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发表时间：
2012-09-15
期刊：
影响因子：
6.2
通讯作者：
Varella-Garcia M
中科院分区：
文献类型：
--
作者：
Camidge DR;Theodoro M;Maxson DA;Skokan M;O'Brien T;Lu X;Doebele RC;Barón AE;Varella-Garcia M
FISH使用分离的红色(3‘)和绿色(5’)ALK探针，在ALK+NSCLC中始终显示100%的肿瘤细胞重排。融合和重新排列的信号的拷贝数也会增加。在这里，我们探讨了ALK阳性细胞百分比和信号拷贝数之间的关系，以及它们与ALK抑制反应之间的关系。对90例ALK阳性的非小细胞肺癌患者进行评估。记录阳性细胞百分比、阳性模式(分裂的、单一的红色或两者兼有)和融合、分离的红色和绿色信号的拷贝数。30名患者接受了克里佐替尼治疗。单个红色信号拷贝数的增加(导致单个红色和分裂的阳性模式)与更高的ALK+细胞百分比相关(r=0.743，p=0.0001)。平均融合拷贝数与孤立红色信号拷贝数呈负相关(r=−0.409，p=0.0001)。无论是阳性细胞百分率(r=0.192，p=0.30)，还是分离红色拷贝数(r=0.274，p=0.195)，均与用药后肿瘤最大缩小率无关。关键ALK信号拷贝数的增加与阳性细胞百分比之间的强烈关联表明，ALK+肿瘤细胞100%的阳性率是由技术因素造成的，而不是生物学因素。在ALK+肿瘤中，无论是阳性细胞百分比还是信号拷贝数似乎都不是预测ALK抑制的益处的信息性变量。融合的红色拷贝数和分离的红色拷贝数之间的反向关系表明，ALK+可能是在显著的染色体新染色体发生之前发展起来的一种独特的近二倍体NSCLC亚型。
FISH, using break-apart red (3’) and green (5’) ALK probes, consistently shows rearrangements in < 100% of tumor cells in ALK+ NSCLC. Increased copy numbers of fused and rearranged signals also occur. Here we explore correlations between the percentage of ALK positive cells and signal copy number and their association with response to ALK inhibition. Ninety ALK + NSCLC cases were evaluated. The percentage of positive cells, pattern of positivity (split, single red, or both) and copy number of fused, isolated red and green signals were recorded. Thirty patients had received crizotinib. Increased isolated red signal copy number (contributing to both single red and split patterns of positivity) correlated with a higher percentage of ALK+ cells (r = 0.743, p = <0.0001). Mean fused copy number was negatively associated with isolated red signal copy number (r = −0.409, p = <0.0001). Neither percentage cells positive (r = 0.192, p = 0.3), nor copy number of isolated red (r = 0.274, p = 0.195) correlated with maximal tumor shrinkage with crizotinib. The strong association between increased copy number of of key ALK signals and percentage positive cells suggests that the <100% rate of cellular positivity in ALK+ tumors is due to technical factors not biology. In ALK+ tumors, neither percentage cells positive, nor signal copy number appear to be informative variables for predicting benefit from ALK inhibition. The inverse relationship between fused and isolated red copy number suggests ALK+ may be a distinct ‘near diploid’ subtype of NSCLC developing before significant chromosomal aneusomy occurs.
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影响因子：
6
作者：
Martelli, Maria Paola;Sozzi, Gabriella;Falini, Brunangelo
通讯作者：
Falini, Brunangelo
DOI：
10.1097/jto.0b013e3181fb7cd6
发表时间：
2011-01
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Salido M;Pijuan L;Martínez-Avilés L;Galván AB;Cañadas I;Rovira A;Zanui M;Martínez A;Longarón R;Sole F;Serrano S;Bellosillo B;Wynes MW;Albanell J;Hirsch FR;Arriola E
通讯作者：
Arriola E
DOI：
10.1158/1078-0432.ccr-10-0851
发表时间：
2010-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Camidge DR;Kono SA;Flacco A;Tan AC;Doebele RC;Zhou Q;Crino L;Franklin WA;Varella-Garcia M
通讯作者：
Varella-Garcia M
影响因子：
11.5
作者：
Takeuchi, Kengo;Choi, Young Lim;Mano, Hiroyuki
通讯作者：
Mano, Hiroyuki
DOI：
10.1056/nejmoa1006448
发表时间：
2010-10-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kwak EL;Bang YJ;Camidge DR;Shaw AT;Solomon B;Maki RG;Ou SH;Dezube BJ;Jänne PA;Costa DB;Varella-Garcia M;Kim WH;Lynch TJ;Fidias P;Stubbs H;Engelman JA;Sequist LV;Tan W;Gandhi L;Mino-Kenudson M;Wei GC;Shreeve SM;Ratain MJ;Settleman J;Christensen JG;Haber DA;Wilner K;Salgia R;Shapiro GI;Clark JW;Iafrate AJ
通讯作者：
Iafrate AJ