From the Department of Pathology, University of Texas Health Sciences Center, San Antonio (Drs Zhang and Jagirdar); the Department of Anatomic and Clinical Pathology, South Texas Veterans Health Care System, San Antonio (Dr Tio); and the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Drs McQuitty, Olsen, and Cagle and Ms Hendrickson). Dr McQuitty is now with the Department of Pathology and Immunology, Baylor College of Medicine, Houston.
Arch Pathol Lab Med. 2014 Mar;138(3):390-4. doi: 10.5858/arpa.2013-0225-OA. Epub 2013 Jun 26.
Lung cancer is the leading cause of cancer deaths in the United States and worldwide. Biomarker testing is critical to personalized therapy in lung adenocarcinoma and has been extensively investigated in non-Hispanic whites, Asians, and African Americans. However, little information addresses the underlying genetic changes in lung adenocarcinoma among Hispanic patients in the United States.
To identify targetable biomarkers other than EGFR and EML4-ALK in Hispanic patients with lung adenocarcinoma.
We tested DNA extracted from 85 lung adenocarcinoma specimens collected from 40 Hispanic and 43 non-Hispanic white patients for previously reported mutations in KRAS, MET, BRAF, mTOR, STAT3, JAK2, PIK3CA, AKT1 through AKT3, and PTEN with a custom Sequenom massARRAY assay (Sequenom, San Diego, California).
Mutations in KRAS were identified in 11 cases (13%; 6 Hispanic [7%], 5 non-Hispanic white [6%]) and had no correlation with sex, age, or smoking history. Mutations in PIK3CA were identified in 2 of the 40 Hispanic patients (5%), including one patient (2.5%) with a concurrent KRAS mutation. The tumors were wild type for all other genes tested.
Targetable biomarkers other than EGFR and EML4-ALK were identified in 7 of the 40 Hispanic patients (18%) and 5 of the 43 non-Hispanic white patients (12%), suggesting a similar mutational frequency. Our highly multiplexed genotyping assay detected actionable mutations in 14% (12 of 83) more patients than would have been identified by EGFR and EML4-ALK testing alone.
肺癌是美国和全球癌症死亡的主要原因。生物标志物检测对肺腺癌的个体化治疗至关重要,已在非西班牙裔白种人、亚洲人和非裔美国人中进行了广泛研究。然而,关于美国西班牙裔患者肺腺癌的潜在遗传变化的信息很少。
鉴定除 EGFR 和 EML4-ALK 以外的可靶向生物标志物,用于治疗西班牙裔肺腺癌患者。
我们使用定制的 Sequenom 质谱阵列(Sequenom,加利福尼亚州圣地亚哥)测试了从 40 名西班牙裔和 43 名非西班牙裔白人患者中收集的 85 个肺腺癌标本中提取的 DNA,以检测先前报道的 KRAS、MET、BRAF、mTOR、STAT3、JAK2、PIK3CA、AKT1 至 AKT3 和 PTEN 中的突变。
在 11 例(13%;6 例西班牙裔[7%],5 例非西班牙裔白人[6%])中发现了 KRAS 突变,且与性别、年龄或吸烟史无关。在 40 名西班牙裔患者中有 2 例(5%)存在 PIK3CA 突变,其中 1 例(2.5%)同时存在 KRAS 突变。其他所有测试基因的肿瘤均为野生型。
在 40 名西班牙裔患者中的 7 例(18%)和 43 名非西班牙裔白人患者中的 5 例(12%)中发现了除 EGFR 和 EML4-ALK 以外的可靶向生物标志物,表明突变频率相似。我们的高通量基因分型检测比单独进行 EGFR 和 EML4-ALK 检测发现了 14%(12/83)更多的可治疗性突变。