Genomic and mutational profiling to assess clonal relationships between multiple non-small cell lung cancers.
Genomic and mutational profiling to assess clonal relationships between multiple non-small cell lung cancers.
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DOI：
10.1158/1078-0432.ccr-09-0594
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发表时间：
2009-08-15
期刊：
影响因子：
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通讯作者：
Begg CB
中科院分区：
文献类型：
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作者：
Girard N;Ostrovnaya I;Lau C;Park B;Ladanyi M;Finley D;Deshpande C;Rusch V;Orlow I;Travis WD;Pao W;Begg CB
在多发性非小细胞肺癌（NSCLC）的情况下，临床医生必须决定患者是否有独立的肿瘤或转移，并相应地调整治疗。目前使用Martini和Melamed标准做出决定，该标准主要基于肿瘤位置和组织学类型。新的基因组工具可以提高评估肿瘤克隆性的能力。我们从至少接受过两次手术的假定独立NSCLC患者中获得新鲜冷冻的肿瘤标本。我们进行了阵列比较基因组杂交（aCGH），选择基因的突变谱，并详细的临床病理学审查。我们分析了来自20名患者的总共42个肿瘤（6名患者具有同步肿瘤; 14名患者具有异时性肿瘤; 24个潜在肿瘤对比较）; 22个肿瘤对可通过aCGH评估。令人惊讶的是，基于基因组分析的分类在4次（18%）比较中与临床病理诊断相矛盾，在1例诊断为转移的病例中鉴定出独立的原发灶，在3例诊断为独立原发灶的病例中鉴定出转移灶。在后3例中观察到匹配的体细胞点突变。基于aCGH，另外4个肿瘤配对被指定为“不确定”结果;然而，在这些肿瘤配对中也发现了匹配的体细胞点突变。通过aCGH被视为独立原发的肿瘤对中没有一个携带匹配的突变。基因组分析可以帮助区分克隆性肿瘤和独立的原发性肿瘤。快速，廉价和可靠的分子工具的发展可能会允许细化目前在这种情况下使用的临床病理标准。
In cases of multiple non-small cell lung cancer (NSCLC), clinicians must decide whether patients have independent tumors or metastases and tailor treatment accordingly. Decisions are currently made using the Martini and Melamed criteria, which are mostly based on tumor location and histological type. New genomic tools could improve the ability to assess tumor clonality. We obtained fresh-frozen tumors specimens from patients who underwent surgery on at least two occasions for presumptively independent NSCLC. We performed array comparative genomic hybridization (aCGH), mutational profiling of select genes, and detailed clinico-pathological review. We analyzed a total of 42 tumors from 20 patients (6 patients with synchronous tumors; 14 patients with metachronous tumors; 24 potential tumor pair comparisons); 22 tumor pairs were evaluable by aCGH. Surprisingly, classification based upon genomic profiling contradicted the clinico-pathologic diagnosis in 4 (18%) of the comparisons, identifying independent primaries in one case diagnosed as metastasis and metastases in 3 cases diagnosed as independent primaries. Matching somatic point mutations were observed in these latter 3 cases. Another 4 tumor pairings were assigned an “equivocal” result based on aCGH; however, matching somatic point mutations were also found in these tumor pairs. None of the tumor pairs deemed independent primaries by aCGH harbored matching mutations. Genomic analysis can help distinguish clonal tumors from independent primaries. The development of rapid, inexpensive and reliable molecular tools may allow for refinement of clinico-pathologic criteria currently used in this setting.