Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The lung cancer mutation consortium experience

Lynette M. Sholl, Dara L. Aisner, Marileila Varella-Garcia, Lynne D. Berry, Dora Dias-Santagata, Ignacio I. Wistuba, Heidi Chen, Junya Fujimoto, Kelly Kugler, Wilbur A. Franklin, A. John Iafrate, Marc Ladanyi, Mark G. Kris, Bruce E. Johnson, Paul A. Bunn, John D. Minna, David J. Kwiatkowski

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

Introduction: Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing and clinicopathologic correlations are presented. Methods: Mutation testing in at least one of the eight genes (epidermal growth factor receptor [EGFR], KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, and PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing+/- peptide nucleic acid and/or sizing assays, along with anaplastic lymphoma kinase (ALK) and/or MET fluorescence in situ hybridization, were performed in six labs on 1007 patients from 14 institutions. Results: In all, 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26% and 35% of cases compared with 5% of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22%, 25%, 8.5%, and 2.4% of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never-smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never-smoking status and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never-smoking status. Two mutations were seen in 2.7% of samples, all but one of which involved one or more of PIK3CA, ALK, or MET. Conclusion: Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations.

Original languageEnglish (US)
Pages (from-to)768-777
Number of pages10
JournalJournal of Thoracic Oncology
Volume10
Issue number5
DOIs
StatePublished - May 30 2015

Fingerprint

Lung Neoplasms
Mutation
Smoking
Neoplasm Metastasis
Epidermal Growth Factor Receptor
Peptide Nucleic Acids
erbB-1 Genes
Adenocarcinoma of lung
Bone Diseases
Mutation Rate
Standard of Care
Fluorescence In Situ Hybridization
Cell Biology
Molecular Biology
Mass Spectrometry
Biopsy
anaplastic lymphoma kinase
Liver
Genes

Keywords

  • FISH
  • Genotyping
  • LCMC
  • Lung adenocarcinoma
  • Mutation

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Sholl, L. M., Aisner, D. L., Varella-Garcia, M., Berry, L. D., Dias-Santagata, D., Wistuba, I. I., ... Kwiatkowski, D. J. (2015). Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The lung cancer mutation consortium experience. Journal of Thoracic Oncology, 10(5), 768-777. https://doi.org/10.1097/JTO.0000000000000516

Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma : The lung cancer mutation consortium experience. / Sholl, Lynette M.; Aisner, Dara L.; Varella-Garcia, Marileila; Berry, Lynne D.; Dias-Santagata, Dora; Wistuba, Ignacio I.; Chen, Heidi; Fujimoto, Junya; Kugler, Kelly; Franklin, Wilbur A.; Iafrate, A. John; Ladanyi, Marc; Kris, Mark G.; Johnson, Bruce E.; Bunn, Paul A.; Minna, John D.; Kwiatkowski, David J.

In: Journal of Thoracic Oncology, Vol. 10, No. 5, 30.05.2015, p. 768-777.

Research output: Contribution to journalArticle

Sholl, LM, Aisner, DL, Varella-Garcia, M, Berry, LD, Dias-Santagata, D, Wistuba, II, Chen, H, Fujimoto, J, Kugler, K, Franklin, WA, Iafrate, AJ, Ladanyi, M, Kris, MG, Johnson, BE, Bunn, PA, Minna, JD & Kwiatkowski, DJ 2015, 'Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The lung cancer mutation consortium experience', Journal of Thoracic Oncology, vol. 10, no. 5, pp. 768-777. https://doi.org/10.1097/JTO.0000000000000516
Sholl, Lynette M. ; Aisner, Dara L. ; Varella-Garcia, Marileila ; Berry, Lynne D. ; Dias-Santagata, Dora ; Wistuba, Ignacio I. ; Chen, Heidi ; Fujimoto, Junya ; Kugler, Kelly ; Franklin, Wilbur A. ; Iafrate, A. John ; Ladanyi, Marc ; Kris, Mark G. ; Johnson, Bruce E. ; Bunn, Paul A. ; Minna, John D. ; Kwiatkowski, David J. / Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma : The lung cancer mutation consortium experience. In: Journal of Thoracic Oncology. 2015 ; Vol. 10, No. 5. pp. 768-777.
@article{68a280ebdb394d69927eba75217f1f63,
title = "Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The lung cancer mutation consortium experience",
abstract = "Introduction: Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing and clinicopathologic correlations are presented. Methods: Mutation testing in at least one of the eight genes (epidermal growth factor receptor [EGFR], KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, and PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing+/- peptide nucleic acid and/or sizing assays, along with anaplastic lymphoma kinase (ALK) and/or MET fluorescence in situ hybridization, were performed in six labs on 1007 patients from 14 institutions. Results: In all, 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26{\%} and 35{\%} of cases compared with 5{\%} of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22{\%}, 25{\%}, 8.5{\%}, and 2.4{\%} of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never-smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never-smoking status and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never-smoking status. Two mutations were seen in 2.7{\%} of samples, all but one of which involved one or more of PIK3CA, ALK, or MET. Conclusion: Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations.",
keywords = "FISH, Genotyping, LCMC, Lung adenocarcinoma, Mutation",
author = "Sholl, {Lynette M.} and Aisner, {Dara L.} and Marileila Varella-Garcia and Berry, {Lynne D.} and Dora Dias-Santagata and Wistuba, {Ignacio I.} and Heidi Chen and Junya Fujimoto and Kelly Kugler and Franklin, {Wilbur A.} and Iafrate, {A. John} and Marc Ladanyi and Kris, {Mark G.} and Johnson, {Bruce E.} and Bunn, {Paul A.} and Minna, {John D.} and Kwiatkowski, {David J.}",
year = "2015",
month = "5",
day = "30",
doi = "10.1097/JTO.0000000000000516",
language = "English (US)",
volume = "10",
pages = "768--777",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "5",

}

TY - JOUR

T1 - Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma

T2 - The lung cancer mutation consortium experience

AU - Sholl, Lynette M.

AU - Aisner, Dara L.

AU - Varella-Garcia, Marileila

AU - Berry, Lynne D.

AU - Dias-Santagata, Dora

AU - Wistuba, Ignacio I.

AU - Chen, Heidi

AU - Fujimoto, Junya

AU - Kugler, Kelly

AU - Franklin, Wilbur A.

AU - Iafrate, A. John

AU - Ladanyi, Marc

AU - Kris, Mark G.

AU - Johnson, Bruce E.

AU - Bunn, Paul A.

AU - Minna, John D.

AU - Kwiatkowski, David J.

PY - 2015/5/30

Y1 - 2015/5/30

N2 - Introduction: Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing and clinicopathologic correlations are presented. Methods: Mutation testing in at least one of the eight genes (epidermal growth factor receptor [EGFR], KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, and PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing+/- peptide nucleic acid and/or sizing assays, along with anaplastic lymphoma kinase (ALK) and/or MET fluorescence in situ hybridization, were performed in six labs on 1007 patients from 14 institutions. Results: In all, 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26% and 35% of cases compared with 5% of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22%, 25%, 8.5%, and 2.4% of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never-smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never-smoking status and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never-smoking status. Two mutations were seen in 2.7% of samples, all but one of which involved one or more of PIK3CA, ALK, or MET. Conclusion: Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations.

AB - Introduction: Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing and clinicopathologic correlations are presented. Methods: Mutation testing in at least one of the eight genes (epidermal growth factor receptor [EGFR], KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, and PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing+/- peptide nucleic acid and/or sizing assays, along with anaplastic lymphoma kinase (ALK) and/or MET fluorescence in situ hybridization, were performed in six labs on 1007 patients from 14 institutions. Results: In all, 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26% and 35% of cases compared with 5% of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22%, 25%, 8.5%, and 2.4% of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never-smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never-smoking status and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never-smoking status. Two mutations were seen in 2.7% of samples, all but one of which involved one or more of PIK3CA, ALK, or MET. Conclusion: Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations.

KW - FISH

KW - Genotyping

KW - LCMC

KW - Lung adenocarcinoma

KW - Mutation

UR - http://www.scopus.com/inward/record.url?scp=84938274454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938274454&partnerID=8YFLogxK

U2 - 10.1097/JTO.0000000000000516

DO - 10.1097/JTO.0000000000000516

M3 - Article

C2 - 25738220

AN - SCOPUS:84938274454

VL - 10

SP - 768

EP - 777

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 5

ER -