Moonsik Kim1, Yeon Seung Chung1, Kyoung A Kim1, Hyo Sup Shim2. 1. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea shimhs@yuhs.ac.
Abstract
BACKGROUND/AIM: In recent years, the genomic landscape of neuroendocrine tumors (NETs) of the lung has been investigated. However, more data are necessary to elucidate the heterogeneous nature of NETs, especially in East Asian patients. PATIENTS AND METHODS: A total of 64 patients who underwent surgical resection for lung NETs [26 typical or atypical carcinoid tumors, 21 large-cell neuroendocrine carcinomas (LCNECs), and 19 small-cell lung carcinomas (SCLCs)] were enrolled, and samples from 46 patients were subjected to targeted next-generation sequencing. RESULTS: Co-mutations of tumor protein p53 (TP53) and RB transcriptional corepressor 1 (RB1) were detected in 15%, 42%, and 93% of carcinoid tumors, LCNECs, and SCLCs, respectively. Oncogenic or targetable genetic alterations identified in this study included mutations of KRAS proto-oncogene (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), ALK receptor tyrosine kinase (ALK), mitogen-activated protein kinase kinase 1 (MAP2K1), and isocitrate dehydrogenase 1 (IDH1), as well as amplifications of erb-b2 receptor tyrosine kinase 2 (ERBB2), fibroblast growth factor receptor 1 (FGFR1), CD274 molecule (CD274), and MYCN proto-oncogene (MYCN). These alterations were more frequently found in high-grade NETs than in carcinoid tumors (33.3% vs. 7.7%). Programmed cell death-ligand 1 expression was strongly associated with the LCNEC subtype among NETs (p=0.002). CONCLUSION: The mutational status of TP53 and RB1 was significantly associated with NET subtypes in East Asian patients. Targeted therapy or immunotherapy may serve as a treatment option in a subset of patients with high-grade NETs. Copyright
BACKGROUND/AIM: In recent years, the genomic landscape of neuroendocrine tumors (NETs) of the lung has been investigated. However, more data are necessary to elucidate the heterogeneous nature of NETs, especially in East Asian patients. PATIENTS AND METHODS: A total of 64 patients who underwent surgical resection for lung NETs [26 typical or atypical carcinoid tumors, 21 large-cell neuroendocrine carcinomas (LCNECs), and 19 small-cell lung carcinomas (SCLCs)] were enrolled, and samples from 46 patients were subjected to targeted next-generation sequencing. RESULTS: Co-mutations of tumor protein p53 (TP53) and RB transcriptional corepressor 1 (RB1) were detected in 15%, 42%, and 93% of carcinoid tumors, LCNECs, and SCLCs, respectively. Oncogenic or targetable genetic alterations identified in this study included mutations of KRAS proto-oncogene (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), ALK receptor tyrosine kinase (ALK), mitogen-activated protein kinase kinase 1 (MAP2K1), and isocitrate dehydrogenase 1 (IDH1), as well as amplifications of erb-b2 receptor tyrosine kinase 2 (ERBB2), fibroblast growth factor receptor 1 (FGFR1), CD274 molecule (CD274), and MYCN proto-oncogene (MYCN). These alterations were more frequently found in high-grade NETs than in carcinoid tumors (33.3% vs. 7.7%). Programmed cell death-ligand 1 expression was strongly associated with the LCNEC subtype among NETs (p=0.002). CONCLUSION: The mutational status of TP53 and RB1 was significantly associated with NET subtypes in East Asian patients. Targeted therapy or immunotherapy may serve as a treatment option in a subset of patients with high-grade NETs. Copyright
Authors: Sylvie Lantuejoul; Ming Sound-Tsao; Wendy A Cooper; Nicolas Girard; Fred R Hirsch; Anja C Roden; Fernando Lopez-Rios; Deepali Jain; Teh-Ying Chou; Noriko Motoi; Keith M Kerr; Yasushi Yatabe; Elisabeth Brambilla; John Longshore; Mauro Papotti; Lynette M Sholl; Erik Thunnissen; Natasha Rekhtman; Alain Borczuk; Lukas Bubendorf; Yuko Minami; Mary Beth Beasley; Johan Botling; Gang Chen; Jin-Haeng Chung; Sanja Dacic; David Hwang; Dongmei Lin; Andre Moreira; Andrew G Nicholson; Masayuki Noguchi; Giuseppe Pelosi; Claudia Poleri; William Travis; Akihiko Yoshida; Jillian B Daigneault; Ignacio I Wistuba; Mari Mino-Kenudson Journal: J Thorac Oncol Date: 2019-12-20 Impact factor: 15.609
Authors: B C M Hermans; J L Derks; E Thunnissen; R J van Suylen; M A den Bakker; H J M Groen; E F Smit; R A Damhuis; E C van den Broek; C M Stallinga; G M Roemen; E J M Speel; A-M C Dingemans Journal: Lung Cancer Date: 2019-02-21 Impact factor: 5.705
Authors: Charles M Rudin; John T Poirier; Lauren Averett Byers; Caroline Dive; Afshin Dowlati; Julie George; John V Heymach; Jane E Johnson; Jonathan M Lehman; David MacPherson; Pierre P Massion; John D Minna; Trudy G Oliver; Vito Quaranta; Julien Sage; Roman K Thomas; Christopher R Vakoc; Adi F Gazdar Journal: Nat Rev Cancer Date: 2019-05 Impact factor: 60.716
Authors: Wei Zhang; Luc Girard; Yu-An Zhang; Tomohiro Haruki; Mahboubeh Papari-Zareei; Victor Stastny; Hans K Ghayee; Karel Pacak; Trudy G Oliver; John D Minna; Adi F Gazdar Journal: Transl Lung Cancer Res Date: 2018-02
Authors: Lynnette Fernandez-Cuesta; Martin Peifer; Xin Lu; Ruping Sun; Luka Ozretić; Danila Seidal; Thomas Zander; Frauke Leenders; Julie George; Christian Müller; Ilona Dahmen; Berit Pinther; Graziella Bosco; Kathryn Konrad; Janine Altmüller; Peter Nürnberg; Viktor Achter; Ulrich Lang; Peter M Schneider; Magdalena Bogus; Alex Soltermann; Odd Terje Brustugun; Åslaug Helland; Steinar Solberg; Marius Lund-Iversen; Sascha Ansén; Erich Stoelben; Gavin M Wright; Prudence Russell; Zoe Wainer; Benjamin Solomon; John K Field; Russell Hyde; Michael Pa Davies; Lukas C Heukamp; Iver Petersen; Sven Perner; Christine Lovly; Federico Cappuzzo; William D Travis; Jürgen Wolf; Martin Vingron; Elisabeth Brambilla; Stefan A Haas; Reinhard Buettner; Roman K Thomas Journal: Nat Commun Date: 2014-03-27 Impact factor: 14.919
Authors: Guido Rindi; David S Klimstra; Behnoush Abedi-Ardekani; Sylvia L Asa; Frederik T Bosman; Elisabeth Brambilla; Klaus J Busam; Ronald R de Krijger; Manfred Dietel; Adel K El-Naggar; Lynnette Fernandez-Cuesta; Günter Klöppel; W Glenn McCluggage; Holger Moch; Hiroko Ohgaki; Emad A Rakha; Nicholas S Reed; Brian A Rous; Hironobu Sasano; Aldo Scarpa; Jean-Yves Scoazec; William D Travis; Giovanni Tallini; Jacqueline Trouillas; J Han van Krieken; Ian A Cree Journal: Mod Pathol Date: 2018-08-23 Impact factor: 7.842