LCMC: Lung Cancer Mutation Consortium

The consortium's homepage is at LungCancerResearchFoundation.org. LCMC4 is active. VBDCC personnel previously contributed their expertise and services to LCMC1 and LCMC2, with the Vanderbilt Center for Quantitative Sciences (CQS) serving as LCMC's statistical data coordinating center since the program's inception in 2009.

The LCMC consists of more than 15 institutions with a key interest in lung cancer. Member institutions enroll patients with advanced adenocarcinoma of the lung to complete comprehensive molecular characterization of the ADC and thereby direct each patient to targeted therapy as available and appropriate to any genetic changes detected.

LCMC4: The LCRF LEADER Neoadjuvant Screening Trial.

LEADER stands for LCMC4 Evaluation of Actionable Drivers in EaRly Stage Lung Cancer.

Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs (LCMC1)

The Impact of Smoking and TP53 Mutations in Lung Adenocarcinoma Patients with Targetable Mutations (LCMC2)

As the statistical data coordinating center for LCMC1 and LCMC2, we developed a web-based data management application to capture patient clinical, pathological, FISH, and IHC data; we also were responsible for integrating these data with sequence data (SNaPshot, Sequenom, Sanger, or NGS) captured in the GeneInsight application (hosted at Harvard University) to prepare routine data reports, as well as providing data analysis and results interpretation. 

CQS still serves as the curator of the finalized datasets, which continue to be queried for various research questions. Flagship LCMC papers have been published in JAMA (Kris et al. 2014) and the Journal of Thoracic Oncology (Sholl et al. 2015), and the final curated dataset has supported numerous additional publications (e.g., Boyle et al. 2019; Guo et al. 2019; El Osta et al. 2019; Aisner et al. 2018; Pillai et al. 2017; Noonan et al. 2016; Steuer et al. 2016; Ohashi et al. 2013). 

The LCMC was initially funded under a Grand Opportunity (GO) grant (RC2 CA148394), with LCMC2 continuing under sponsorship from the National Lung Cancer Partnership (NLCP; now Free to Breathe), LCMC3 in partnership with Genentech, and LCMC4 launched under the auspices of the Lung Cancer Research Foundation (LCRF). 

References

Aisner DL, Sholl LM, Berry LD, et al. The impact of smoking and TP53 mutations in lung adenocarcinoma patients with targetable mutations—The Lung Cancer Mutation Consortium (LCMC2). Clin Cancer Res. 2018 Mar 1;24(5):1038-1047. doi:10.1158/1078-0432.CCR-17-2289. Epub 2017 Dec 7. PMID:29217530; PMCID:PMC7008001.

Boyle TA, Khalil FK, Mino-Kenudson M, et al. Round robin evaluation of MET protein expression in lung adenocarcinomas improves interobserver concordance. Appl Immunohistochem Mol Morphol. 2020 Oct;28(9):669-677. doi:10.1097/PAI.0000000000000810. PMID:31876606; PMCID:PMC7242128.

El Osta B, Behera M, Kim S, et al. Characteristics and outcomes of patients with metastatic KRAS-mutant lung adenocarcinomas: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2019 May;14(5):876-889. doi:10.1016/j.jtho.2019.01.020. Epub 2019 Feb 5. PMID:30735816; PMCID:PMC8108452.

Guo R, Berry LD, Aisner DL, et al. MET IHC is a poor screen for MET amplification or MET exon 14 mutations in lung adenocarcinomas: Data from a tri-institutional cohort of the Lung Cancer Mutation Consortium. J Thorac Oncol. 2019 Sep;14(9):1666-1671. doi:10.1016/j.jtho.2019.06.009. Epub 2019 Jun 20. PMID:31228623; PMCID:PMC6708730.

Kris MG, Johnson BE, Berry LD, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014 May 21;311(19):1998-2006. doi:10.1001/jama.2014.3741. PMID:24846037; PMCID:PMC4163053.

Noonan SA, Berry L, Lu X, et al. Identifying the appropriate FISH criteria for defining MET copy number-driven lung adenocarcinoma through oncogene overlap analysis. J Thorac Oncol. 2016 Aug;11(8):1293-1304. doi:10.1016/j.jtho.2016.04.033. Epub 2016 Jun 1. PMID:27262212; PMCID:PMC5404374.

Ohashi K et al. Characteristics of lung cancers harboring NRAS mutations. Clin Cancer Res. 2013 May 1;19(9):2584-91. doi:10.1158/1078-0432.CCR-12-3173. Epub 2013 Mar 20. PMID:23515407; PMCID:PMC3643999.

Pillai RN, Behera M, Berry LD, et al. HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium. Cancer. 2017 Nov 1;123(21):4099-4105. doi:10.1002/cncr.30869. Epub 2017 Jul 25. PMID:28743157; PMCID:PMC5650517.

Sholl LM, Aisner DL, Varella-Garcia M, et al. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015 May;10(5):768-777. doi:10.1097/JTO.0000000000000516. PMID:25738220; PMCID:PMC4410843.

Steuer CE, Behera M, Berry L, et al. Role of race in oncogenic driver prevalence and outcomes in lung adenocarcinoma: Results from the Lung Cancer Mutation Consortium. Cancer. 2016 Mar 1;122(5):766-72. doi:10.1002/cncr.29812. Epub 2015 Dec 22. PMID:26695526; PMCID:PMC5038591.