Abstract 5134: Landscape of genomic alterations across solid tumors based on a comprehensive clinical sequencing analysis of 5355 Chinese cancer patients
Authors: Yao Ming , Wang Minghui , Chen Mingwu , Shou Tao , Cao Jingyu , Chen Hui , Wang Aodi , Chen Lijuan , Hu Jinwei , Zhang Shuirong , Wang Kai 
Published: August 2019

Background: Precision oncology highlights the individualization of diagnosis, prognosis and treatment based on molecular stratification of cancer patients (pts). Genetic patterns in many types of cancer vary among geographical regions, leading to variation in evidence-based recommendations for clinical management of pts. Genomic alterations (GAs) of solid tumors from Chinese pts have not been fully studied across all cancer types.

Methods: Tumor tissues and matched blood from 5355 Chinese pts were collected and sequenced by a next generation sequencing based 450-gene panel assay. About 60% of the samples were FFPE tissues. In our study, 59% were males and 41% were females with a median age of 58 years old (range 1-92). The major cancer types were NSCLC (36%), CRC (8%), HCC (7%), gastric cancer (5%), pancreatic cancer (5%), and also cholangiocarcinoma, esophageal carcinoma, SCLC, gallbladder carcinoma, ovarian cancer, breast cancer, head and neck cancer, sarcoma, renal carcinoma, uterine neoplasms and others. 1% were pediatric patients . Single base substitutions, short and long insertions/deletions (indels), copy number alterations (CNA), fusions/rearrangements, TMB and MSI status were assessed by NGS.

Results: On average, our study identified 7 mutations per patient. Gene rearrangements and long indels (50bp - 2k) were detected in 15% and 5% of the cancers. In total, 58% of pts harbored GAs in druggable genes defined as targets of FDA approved drugs. Highest mutation frequencies were found in TP53 (60%), EGFR (23%), KRAS (18%), CDKN2A (13%), TERT (12%), PIK3CA (11%), APC (11%), LRP1B (10%), ARID1A (9%), and RB1 (8%) across all tumor types. The frequency of other druggable genes included BRCA1/2 (5%), BRAF (3%), HER2 amplifications (3%), MET amplifications (2%), ALK fusions (2%), RET fusions (0.7%), ROS1 fusions (0.7%), FGFR fusions (0.7%), NTRK fusion (0.6%). Frequency of GAs in druggable genes varied among different tumor types. For instance, EGFR mutations occurred in 49% of NSCLC, 7% of SCLC, 2% of gastric cancer, and 2% of CRC. NTRK fusions enriched in sarcoma (4%), gastric cancer (2%) and CRC (1%). The median TMB of the whole cohort was 4.6 muts/Mb and 6% had TMB higher than 20 muts/Mb. Top 3 tumors with highest median TMB were SCLC, CRC and gastric cancer, while pancreatic cancer and sarcoma had low TMB. As a pan-cancer biomarker for immunotherapy, pts with MSI-H accounted for 1.3% of solid tumors, including 9% of uterine neoplasms, 8% of CRC, 6% of gastric cancer and 2% of ICC.

Conclusions: In summary, we have constructed a large-scale data set including somatic mutations, CNAs, fusions/rearrangements, TMB and MSI status from 5355 Chinese pts with more than 19 tumor types, which provided an extensive understanding of disease-specific indicators, outcomes and therapeutic strategies for both targeted and immune therapies in Chinese pts.

Citation Format: Ming Yao, Minghui Wang, Mingwu Chen, Tao Shou, Jingyu Cao, Hui Chen, Aodi Wang, Lijuan Chen, Jinwei Hu, Shuirong Zhang, Kai Wang. Landscape of genomic alterations across solid tumors based on a comprehensive clinical sequencing analysis of 5355 Chinese cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5134.