Mitsuhiro Isaka1, Masakuni Serizawa2, Hirotsugu Kenmotsu3, Yasuhiro Koh4, Shoji Takahashi5, Tomohiro Maniwa5, Kazushige Wakuda3, Akira Ono3, Tateaki Naito3, Haruyasu Murakami3, Keita Mori6, Masahiro Endo7, Masato Abe8, Isamu Hayashi8, Takashi Nakajima8, Nobuyuki Yamamoto9, Toshiaki Takahashi3, Yasuhisa Ohde5. 1. Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan. Electronic address: m.isaka@scchr.jp. 2. Drug Discovery and Development Division, Research Institute, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan. 3. Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan. 4. Drug Discovery and Development Division, Research Institute, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan; Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama, Japan. 5. Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan. 6. Clinical Trial Coordination Office, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan. 7. Division of Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan. 8. Division of Pathology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan. 9. Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan; Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama, Japan.
Abstract
BACKGROUND: Amplicon-based massively parallel sequencing (MPS) is an effective platform for identifying clinically actionable mutations across many genes in limited amounts of tissue. Most lung cancers are diagnosed and staged using small tissue samples obtained by transbronchial biopsy (TBB). To determine whether the mutations in TBB specimens detected by amplicon-based MPS reflect those present in the tumors, we compared the mutational profiles of preoperative TBB specimens and corresponding surgically resected specimens. PATIENTS AND METHODS: Fresh-frozen primary tumor specimens from non-small-cell lung cancer patients (n = 46) obtained preoperatively by TBB and during surgical resection were analyzed. The concordance of mutations detected by amplicon-based MPS in the 2 sample types was investigated, and the allele frequency of the mutations common to both specimens from the same patient was determined. RESULTS: An initial assessment of DNA quantity revealed that 46% of the TBB specimens (21 of 46) had less than the lower limit for amplicon-based MPS. These 21 TBB specimens were consequently omitted from the analysis. Of the 29 mutations detected in the TBB and/or surgically resected specimens from 25 patients, 23 were present in both samples, for a concordance rate of 79%. CONCLUSION: Amplicon-based MPS with TBB specimens approximately reflects clinically relevant tumor mutation profiles. However, the rate of TBB specimens with sufficient DNA quantity for amplicon-based MPS was only around 50%. Therefore, surgically resected specimens have a valuable role in exploratory and comprehensive genomic profiling.
BACKGROUND: Amplicon-based massively parallel sequencing (MPS) is an effective platform for identifying clinically actionable mutations across many genes in limited amounts of tissue. Most lung cancers are diagnosed and staged using small tissue samples obtained by transbronchial biopsy (TBB). To determine whether the mutations in TBB specimens detected by amplicon-based MPS reflect those present in the tumors, we compared the mutational profiles of preoperative TBB specimens and corresponding surgically resected specimens. PATIENTS AND METHODS: Fresh-frozen primary tumor specimens from non-small-cell lung cancerpatients (n = 46) obtained preoperatively by TBB and during surgical resection were analyzed. The concordance of mutations detected by amplicon-based MPS in the 2 sample types was investigated, and the allele frequency of the mutations common to both specimens from the same patient was determined. RESULTS: An initial assessment of DNA quantity revealed that 46% of the TBB specimens (21 of 46) had less than the lower limit for amplicon-based MPS. These 21 TBB specimens were consequently omitted from the analysis. Of the 29 mutations detected in the TBB and/or surgically resected specimens from 25 patients, 23 were present in both samples, for a concordance rate of 79%. CONCLUSION: Amplicon-based MPS with TBB specimens approximately reflects clinically relevant tumor mutation profiles. However, the rate of TBB specimens with sufficient DNA quantity for amplicon-based MPS was only around 50%. Therefore, surgically resected specimens have a valuable role in exploratory and comprehensive genomic profiling.
Authors: Verena Sailer; Kenneth Wa Eng; Tuo Zhang; Rohan Bareja; David J Pisapia; Alexandros Sigaras; Bhavneet Bhinder; Alessandro Romanel; David Wilkes; Evan Sticca; Joanna Cyrta; Rema Rao; Sheena Sahota; Chantal Pauli; Shaham Beg; Samaneh Motanagh; Myriam Kossai; Jacqueline Fontunge; Loredana Puca; Hanna Rennert; Jenny Zhaoying Xiang; Noah Greco; Rob Kim; Theresa Y MacDonald; Terra McNary; Mirjam Blattner-Johnson; Marc H Schiffman; Bishoy M Faltas; Jeffrey P Greenfield; David Rickman; Eleni Andreopoulou; Kevin Holcomb; Linda T Vahdat; Douglas S Scherr; Koen van Besien; Christopher E Barbieri; Brian D Robinson; Howard Alan Fine; Allyson J Ocean; Ana Molina; Manish A Shah; David M Nanus; Qiulu Pan; Francesca Demichelis; Scott T Tagawa; Wei Song; Juan Miguel Mosquera; Andrea Sboner; Mark A Rubin; Olivier Elemento; Himisha Beltran Journal: JCO Precis Oncol Date: 2019-09-20
Authors: Raul Caso; James G Connolly; Jian Zhou; Kay See Tan; James J Choi; Gregory D Jones; Brooke Mastrogiacomo; Francisco Sanchez-Vega; Bastien Nguyen; Gaetano Rocco; Daniela Molena; Smita Sihag; Prasad S Adusumilli; Matthew J Bott; David R Jones Journal: NPJ Precis Oncol Date: 2021-07-21