Hongbiao Wang1, Xiaohua Xu2, Lan Luo3, Chunbing Wang4, Zeyong Jiang5, Yingcheng Lin1. 1. Medical Oncology Session No.1, Cancer Hospital of Shantou University Medical College, Shantou, China. 2. Cardiothoracic surgery department, The Second Affiliated Hospital of Shantou University Medical College, Guangzhou, China. 3. Department of Oncology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China. 4. Medical Oncology Department, Cancer Hospital Chinese Academy of Medical Science, Shenzhen, China. 5. Department of Thoracic Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
Abstract
BACKGROUND: Thymic epithelial tumors (TETs) are a heterogeneous group of rare malignancies which may be devastating, difficult to treat, and for which treatment options are limited. Herein, we investigated the comprehensive genomic alterations of TETs in a Chinese population for providing clinical management, especially targeted therapy. METHODS: Comprehensive genomic profiling (CGP) was performed with DNA targeted sequencing of cancer-associated genes (CSYS) from a cohort of 40 Chinese TET patients. TMB was measured by an in-house algorithm. MSI status was inferred based on the MANTIS (Microsatellite Analysis for Normal-Tumor InStability) score. The expression status of PD-L1 was estimated by immunohistochemistry. RESULTS: The mutational profiling of thymomas (Ts) and thymic neuroendocrine tumors (TNETs) showed scattered mutation distributions with no recurrently mutated genes. In contrast, thymic carcinomas (TCs) did show highly recurrent mutations including CDKN2A, CYLD, CDKN2B, and TP53. Among them, CDKN2A and CDKN2B mutations were the top potentially actionable alterations in TCs. PD-L1 expression was mainly present in Ts and TCs, and was predominant in males and smokers. CONCLUSIONS: Our study provided a comprehensive genetic alteration view on the largest Chinese cohort of TETs to date. The results identified different genomic mutational profiles of Ts, TCs, and TNETs, and analyzed potential druggable biomarkers with clinical implications in Chinese TET patients, which provided the evidence for precision medicine of rare TET patients. 2021 Gland Surgery. All rights reserved.
BACKGROUND: Thymic epithelial tumors (TETs) are a heterogeneous group of rare malignancies which may be devastating, difficult to treat, and for which treatment options are limited. Herein, we investigated the comprehensive genomic alterations of TETs in a Chinese population for providing clinical management, especially targeted therapy. METHODS: Comprehensive genomic profiling (CGP) was performed with DNA targeted sequencing of cancer-associated genes (CSYS) from a cohort of 40 Chinese TET patients. TMB was measured by an in-house algorithm. MSI status was inferred based on the MANTIS (Microsatellite Analysis for Normal-Tumor InStability) score. The expression status of PD-L1 was estimated by immunohistochemistry. RESULTS: The mutational profiling of thymomas (Ts) and thymic neuroendocrine tumors (TNETs) showed scattered mutation distributions with no recurrently mutated genes. In contrast, thymic carcinomas (TCs) did show highly recurrent mutations including CDKN2A, CYLD, CDKN2B, and TP53. Among them, CDKN2A and CDKN2B mutations were the top potentially actionable alterations in TCs. PD-L1 expression was mainly present in Ts and TCs, and was predominant in males and smokers. CONCLUSIONS: Our study provided a comprehensive genetic alteration view on the largest Chinese cohort of TETs to date. The results identified different genomic mutational profiles of Ts, TCs, and TNETs, and analyzed potential druggable biomarkers with clinical implications in Chinese TET patients, which provided the evidence for precision medicine of rare TET patients. 2021 Gland Surgery. All rights reserved.
Authors: Arun Rajan; Corey A Carter; Arlene Berman; Liang Cao; Ronan J Kelly; Anish Thomas; Sean Khozin; Ariel Lopez Chavez; Isabella Bergagnini; Barbara Scepura; Eva Szabo; Min-Jung Lee; Jane B Trepel; Sarah K Browne; Lindsey B Rosen; Yunkai Yu; Seth M Steinberg; Helen X Chen; Gregory J Riely; Giuseppe Giaccone Journal: Lancet Oncol Date: 2014-01-15 Impact factor: 41.316
Authors: Milan Radovich; Curtis R Pickering; Ina Felau; Gavin Ha; Hailei Zhang; Heejoon Jo; Katherine A Hoadley; Pavana Anur; Jiexin Zhang; Mike McLellan; Reanne Bowlby; Thomas Matthew; Ludmila Danilova; Apurva M Hegde; Jaegil Kim; Mark D M Leiserson; Geetika Sethi; Charles Lu; Michael Ryan; Xiaoping Su; Andrew D Cherniack; Gordon Robertson; Rehan Akbani; Paul Spellman; John N Weinstein; D Neil Hayes; Ben Raphael; Tara Lichtenberg; Kristen Leraas; Jean Claude Zenklusen; Junya Fujimoto; Cristovam Scapulatempo-Neto; Andre L Moreira; David Hwang; James Huang; Mirella Marino; Robert Korst; Giuseppe Giaccone; Yesim Gokmen-Polar; Sunil Badve; Arun Rajan; Philipp Ströbel; Nicolas Girard; Ming S Tsao; Alexander Marx; Anne S Tsao; Patrick J Loehrer Journal: Cancer Cell Date: 2018-02-12 Impact factor: 31.743
Authors: Jeffrey R Infante; Philippe A Cassier; John F Gerecitano; Petronella O Witteveen; Rashmi Chugh; Vincent Ribrag; Abhijit Chakraborty; Alessandro Matano; Jason R Dobson; Adam S Crystal; Sudha Parasuraman; Geoffrey I Shapiro Journal: Clin Cancer Res Date: 2016-08-19 Impact factor: 12.531
Authors: Amita Patnaik; Lee S Rosen; Sara M Tolaney; Anthony W Tolcher; Jonathan W Goldman; Leena Gandhi; Kyriakos P Papadopoulos; Muralidhar Beeram; Drew W Rasco; John F Hilton; Aejaz Nasir; Richard P Beckmann; Andrew E Schade; Angie D Fulford; Tuan S Nguyen; Ricardo Martinez; Palaniappan Kulanthaivel; Lily Q Li; Martin Frenzel; Damien M Cronier; Edward M Chan; Keith T Flaherty; Patrick Y Wen; Geoffrey I Shapiro Journal: Cancer Discov Date: 2016-05-23 Impact factor: 39.397