title: Comparison of Clinically Relevant Mutation Profiles Between Preoperative Biopsy and Corresponding Surgically Resected Specimens in Japanese Patients With Non-Small-cell Lung Cancer by Amplicon-based Massively Parallel Sequencing.
abstract: 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.
  
  
  
  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.
  
  
  
  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%.
  
  
  
  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.affiliation: Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan. Electronic address: m.isaka@scchr.jp.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Isaka
authors.affiliation: Drug Discovery and Development Division, Research Institute, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Masakuni
authors.initials: M
authors.lastname: Serizawa
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kenmotsu
authors.affiliation: 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.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Maniwa
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Wakuda
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ono
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Tateaki
authors.initials: T
authors.lastname: Naito
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Clinical Trial Coordination Office, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Mori
authors.affiliation: Division of Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Endo
authors.affiliation: Division of Pathology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Abe
authors.affiliation: Division of Pathology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Hayashi
authors.affiliation: Division of Pathology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan; Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Division of Thoracic Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ohde
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005787:Gene Frequency; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011184:Postoperative Period; D057234:Preoperative Period; D015203:Reproducibility of Results
chemical_list: D004273:DNA, Neoplasm
keywords: Amplicon-based massively parallel sequencing; Genetic alterations; NSCLC; Surgical specimens; Transbronchial biopsy specimens