Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative

Sun Min Lim, Eun Young Kim, Hye Ryun Kim, Siraj M. Ali, Joel R. Greenbowe, Hyo Sup Shim, Hyun Chang, Seungtaek Lim, Soonmyung Paik, Byoung Chul Cho

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Identification of clinically relevant oncogenic drivers in advanced cancer is critical in selecting appropriate targeted therapy. Using next-generation sequencing (NGS)-based clinical cancer gene assay, we performed comprehensive genomic profiling (CGP) of advanced cases of lung adenocarcinoma. Methods: Formalin-fixed paraffin-embedded tumors from 51 lung adenocarcinoma patients whose tumors previously tested negative for EGFR/KRAS/ALK by conventional methods were collected, and CGP was performed via hybridization capture of 4,557 exons from 287 cancer-related genes and 47 introns from 19 genes frequently rearranged in cancer. Results: Genomic profiles of all 51 cases were obtained, with a median coverage of 564x and a total of 190 individual genomic alterations (GAs). GAs per specimen was a mean of 3.7 (range 0-10).Cancer genomes are characterized by 50% (80/190) non-synonymous base substitutions, 15% (29/190) insertions or deletion, and 3% (5/190) splice site mutation. TP53 mutation was the most common GAs (15%, n=29/190), followed by CDKN2A homozygous loss (5%, n=10/190), KRAS mutation (4%, n=8/190), EGFR mutation (4%, n=8/190) and MDM2 amplification (2%, n=5/190). As per NCCN guidelines, targetable GAs were identified in 16 patients (31%) (BRAF mutation [n=1], EGFR mutation [n=8], ERBB2 mutation [n=4], MET amplification [n=1], KIF5B-RET rearrangement [n=2], CCDC6-RET rearrangement [n=1], CD74-ROS1 rearrangement [n=1], EZR-ROS1 rearrangement [n=5], and SLC34A2-ROS1 rearrangement [n=1]). Conclusion: Fifty eight percent of patients wild type by standard testing for EGFR/KRAS/ALK have GAs identifiable by CGP that suggest benefit from target therapy. CGP used when standard molecular testing for NSCLC is negative can reveal additional avenues of benefit from targeted therapy.

Original languageEnglish
Pages (from-to)24172-24178
Number of pages7
JournalOncotarget
Volume7
Issue number17
DOIs
Publication statusPublished - 2016 Apr 26

Fingerprint

Mutation
Neoplasm Genes
Neoplasms
Therapeutics
RNA Splice Sites
Adenocarcinoma of lung
Paraffin
Introns
Formaldehyde
Exons
Genome
Guidelines
Genes

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Lim, Sun Min ; Kim, Eun Young ; Kim, Hye Ryun ; Ali, Siraj M. ; Greenbowe, Joel R. ; Shim, Hyo Sup ; Chang, Hyun ; Lim, Seungtaek ; Paik, Soonmyung ; Cho, Byoung Chul. / Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative. In: Oncotarget. 2016 ; Vol. 7, No. 17. pp. 24172-24178.
@article{e848ff17a6be497d8975f22cdd9b1b48,
title = "Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative",
abstract = "Background: Identification of clinically relevant oncogenic drivers in advanced cancer is critical in selecting appropriate targeted therapy. Using next-generation sequencing (NGS)-based clinical cancer gene assay, we performed comprehensive genomic profiling (CGP) of advanced cases of lung adenocarcinoma. Methods: Formalin-fixed paraffin-embedded tumors from 51 lung adenocarcinoma patients whose tumors previously tested negative for EGFR/KRAS/ALK by conventional methods were collected, and CGP was performed via hybridization capture of 4,557 exons from 287 cancer-related genes and 47 introns from 19 genes frequently rearranged in cancer. Results: Genomic profiles of all 51 cases were obtained, with a median coverage of 564x and a total of 190 individual genomic alterations (GAs). GAs per specimen was a mean of 3.7 (range 0-10).Cancer genomes are characterized by 50{\%} (80/190) non-synonymous base substitutions, 15{\%} (29/190) insertions or deletion, and 3{\%} (5/190) splice site mutation. TP53 mutation was the most common GAs (15{\%}, n=29/190), followed by CDKN2A homozygous loss (5{\%}, n=10/190), KRAS mutation (4{\%}, n=8/190), EGFR mutation (4{\%}, n=8/190) and MDM2 amplification (2{\%}, n=5/190). As per NCCN guidelines, targetable GAs were identified in 16 patients (31{\%}) (BRAF mutation [n=1], EGFR mutation [n=8], ERBB2 mutation [n=4], MET amplification [n=1], KIF5B-RET rearrangement [n=2], CCDC6-RET rearrangement [n=1], CD74-ROS1 rearrangement [n=1], EZR-ROS1 rearrangement [n=5], and SLC34A2-ROS1 rearrangement [n=1]). Conclusion: Fifty eight percent of patients wild type by standard testing for EGFR/KRAS/ALK have GAs identifiable by CGP that suggest benefit from target therapy. CGP used when standard molecular testing for NSCLC is negative can reveal additional avenues of benefit from targeted therapy.",
author = "Lim, {Sun Min} and Kim, {Eun Young} and Kim, {Hye Ryun} and Ali, {Siraj M.} and Greenbowe, {Joel R.} and Shim, {Hyo Sup} and Hyun Chang and Seungtaek Lim and Soonmyung Paik and Cho, {Byoung Chul}",
year = "2016",
month = "4",
day = "26",
doi = "10.18632/oncotarget.8138",
language = "English",
volume = "7",
pages = "24172--24178",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "17",

}

Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative. / Lim, Sun Min; Kim, Eun Young; Kim, Hye Ryun; Ali, Siraj M.; Greenbowe, Joel R.; Shim, Hyo Sup; Chang, Hyun; Lim, Seungtaek; Paik, Soonmyung; Cho, Byoung Chul.

In: Oncotarget, Vol. 7, No. 17, 26.04.2016, p. 24172-24178.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative

AU - Lim, Sun Min

AU - Kim, Eun Young

AU - Kim, Hye Ryun

AU - Ali, Siraj M.

AU - Greenbowe, Joel R.

AU - Shim, Hyo Sup

AU - Chang, Hyun

AU - Lim, Seungtaek

AU - Paik, Soonmyung

AU - Cho, Byoung Chul

PY - 2016/4/26

Y1 - 2016/4/26

N2 - Background: Identification of clinically relevant oncogenic drivers in advanced cancer is critical in selecting appropriate targeted therapy. Using next-generation sequencing (NGS)-based clinical cancer gene assay, we performed comprehensive genomic profiling (CGP) of advanced cases of lung adenocarcinoma. Methods: Formalin-fixed paraffin-embedded tumors from 51 lung adenocarcinoma patients whose tumors previously tested negative for EGFR/KRAS/ALK by conventional methods were collected, and CGP was performed via hybridization capture of 4,557 exons from 287 cancer-related genes and 47 introns from 19 genes frequently rearranged in cancer. Results: Genomic profiles of all 51 cases were obtained, with a median coverage of 564x and a total of 190 individual genomic alterations (GAs). GAs per specimen was a mean of 3.7 (range 0-10).Cancer genomes are characterized by 50% (80/190) non-synonymous base substitutions, 15% (29/190) insertions or deletion, and 3% (5/190) splice site mutation. TP53 mutation was the most common GAs (15%, n=29/190), followed by CDKN2A homozygous loss (5%, n=10/190), KRAS mutation (4%, n=8/190), EGFR mutation (4%, n=8/190) and MDM2 amplification (2%, n=5/190). As per NCCN guidelines, targetable GAs were identified in 16 patients (31%) (BRAF mutation [n=1], EGFR mutation [n=8], ERBB2 mutation [n=4], MET amplification [n=1], KIF5B-RET rearrangement [n=2], CCDC6-RET rearrangement [n=1], CD74-ROS1 rearrangement [n=1], EZR-ROS1 rearrangement [n=5], and SLC34A2-ROS1 rearrangement [n=1]). Conclusion: Fifty eight percent of patients wild type by standard testing for EGFR/KRAS/ALK have GAs identifiable by CGP that suggest benefit from target therapy. CGP used when standard molecular testing for NSCLC is negative can reveal additional avenues of benefit from targeted therapy.

AB - Background: Identification of clinically relevant oncogenic drivers in advanced cancer is critical in selecting appropriate targeted therapy. Using next-generation sequencing (NGS)-based clinical cancer gene assay, we performed comprehensive genomic profiling (CGP) of advanced cases of lung adenocarcinoma. Methods: Formalin-fixed paraffin-embedded tumors from 51 lung adenocarcinoma patients whose tumors previously tested negative for EGFR/KRAS/ALK by conventional methods were collected, and CGP was performed via hybridization capture of 4,557 exons from 287 cancer-related genes and 47 introns from 19 genes frequently rearranged in cancer. Results: Genomic profiles of all 51 cases were obtained, with a median coverage of 564x and a total of 190 individual genomic alterations (GAs). GAs per specimen was a mean of 3.7 (range 0-10).Cancer genomes are characterized by 50% (80/190) non-synonymous base substitutions, 15% (29/190) insertions or deletion, and 3% (5/190) splice site mutation. TP53 mutation was the most common GAs (15%, n=29/190), followed by CDKN2A homozygous loss (5%, n=10/190), KRAS mutation (4%, n=8/190), EGFR mutation (4%, n=8/190) and MDM2 amplification (2%, n=5/190). As per NCCN guidelines, targetable GAs were identified in 16 patients (31%) (BRAF mutation [n=1], EGFR mutation [n=8], ERBB2 mutation [n=4], MET amplification [n=1], KIF5B-RET rearrangement [n=2], CCDC6-RET rearrangement [n=1], CD74-ROS1 rearrangement [n=1], EZR-ROS1 rearrangement [n=5], and SLC34A2-ROS1 rearrangement [n=1]). Conclusion: Fifty eight percent of patients wild type by standard testing for EGFR/KRAS/ALK have GAs identifiable by CGP that suggest benefit from target therapy. CGP used when standard molecular testing for NSCLC is negative can reveal additional avenues of benefit from targeted therapy.

UR - http://www.scopus.com/inward/record.url?scp=84966667720&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84966667720&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.8138

DO - 10.18632/oncotarget.8138

M3 - Article

C2 - 26992220

AN - SCOPUS:84966667720

VL - 7

SP - 24172

EP - 24178

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 17

ER -