GRC n°04, Theranoscan, Sorbonne Universités, UPMC Université de Paris 06, Paris.
INSERM U1004, Université de Paris 11, Institut André Wolf, Villejuif Department of Biochemistry and Molecular Biology, AP-HP, Hôpital Paul Brousse, Villejuif.
Ann Oncol. 2015 Aug;26(8):1748-53. doi: 10.1093/annonc/mdv232. Epub 2015 May 12.
Pulmonary sarcomatoid carcinomas (SC) are tumors characterized by poor prognosis and resistance to conventional platinum-based chemotherapy. This study sought to describe the mutational profile of SC using high-throughput genotyping technology.
We used mass spectrometry to test 114 surgical biopsies from 81 patients with SC for 214 mutations affecting 26 oncogenes and tumor suppressor genes.
In total, 75 (92.6%) patients were smokers. Within the total 81 tumors, 67 distinct somatic alterations were identified, with 56 tumors (69.1%) harboring at least one mutation. The most frequent mutations were KRAS (27.2%), EGFR (22.2%), TP53 (22.2%), STK11 (7.4%), NOTCH1 (4.9%), NRAS (4.9%), and PI3KCA (4.9%). The EGFR mutations were almost always rare mutations (89%). In 32 tumors (39.5%), two or more mutations co-existed, with up to four mutations in a single case. In six different cases, comparative genetic analysis of different histological areas from the same tumor (giant, spindle, or epithelial component) revealed a 61% concordance rate for all the mutations with a 10% detection threshold, compared with 91.7% with a 20% detection threshold.
Our results demonstrated a high mutation rate and frequent co-mutations. Despite SC tumors exhibiting a high histological heterogeneity, some intratumoral molecular homogeneity was found. Now with newly developed targeted therapies, SC patients may be eligible for new target mutations, and can now therefore be screened for clinical trials.
肺肉瘤样癌（SC）是一种预后差且对常规铂类化疗耐药的肿瘤。本研究旨在利用高通量基因分型技术描述 SC 的突变特征。
我们使用质谱法对 81 名 SC 患者的 114 例手术活检标本进行了 214 个影响 26 个癌基因和肿瘤抑制基因的突变检测。
共有 75 例（92.6%）患者为吸烟者。在总共 81 例肿瘤中，确定了 67 个不同的体细胞改变，其中 56 例（69.1%）肿瘤携带至少一个突变。最常见的突变是 KRAS（27.2%）、EGFR（22.2%）、TP53（22.2%）、STK11（7.4%）、NOTCH1（4.9%）、NRAS（4.9%）和 PI3KCA（4.9%）。EGFR 突变几乎都是罕见突变（89%）。在 32 例肿瘤（39.5%）中，两个或更多突变共存，在单个病例中最多存在四个突变。在六个不同的病例中，对同一肿瘤的不同组织学区域（巨细胞、梭形或上皮成分）进行比较遗传学分析，在 10%的检测阈值下，所有突变的一致性率为 61%，而在 20%的检测阈值下，一致性率为 91.7%。
我们的结果表明，突变率高且经常发生共突变。尽管 SC 肿瘤表现出高度的组织学异质性，但也发现了一些肿瘤内的分子同质性。现在有了新开发的靶向治疗方法，SC 患者可能有资格获得新的靶突变，因此现在可以筛选他们参加临床试验。
