The underlying tumor genomics of predominant histologic subtypes in lung adenocarcinoma Journal Article
| Authors: | Caso, R.; Sanchez-Vega, F.; Tan, K. S.; Mastrogiacomo, B.; Zhou, J.; Jones, G. D.; Nguyen, B.; Schultz, N.; Connolly, J. G.; Brandt, W. S.; Bott, M. J.; Rocco, G.; Molena, D.; Isbell, J. M.; Liu, Y.; Mayo, M. W.; Adusumilli, P. S.; Travis, W. D.; Jones, D. R. |
| Article Title: | The underlying tumor genomics of predominant histologic subtypes in lung adenocarcinoma |
| Abstract: | Introduction: The purpose of the study is to genomically characterize the biology and related therapeutic opportunities of prognostically important predominant histologic subtypes in lung adenocarcinoma (LUAD). Methods: We identified 604 patients with stage I to III LUAD who underwent complete resection and targeted next-generation sequencing using the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets platform. Tumors were classified according to predominant histologic subtype and grouped by architectural grade (lepidic [LEP], acinar or papillary [ACI/PAP], and micropapillary or solid [MIP/SOL]). Associations among clinicopathologic factors, genomic features, mutational signatures, and recurrence were evaluated within subtypes and, when appropriate, quantified using competing-risks regression, with adjustment for pathologic stage and extent of resection. Results: MIP/SOL tumors had higher tumor mutational burden (p < 0.001), fraction of genome altered (p = 0.001), copy number amplifications (p = 0.021), rate of whole-genome doubling (p = 0.008), and number of oncogenic pathways altered ( p < 0.001) as compared with LEP and ACI/PAP tumors. Across all tumors, mutational signatures attributed to APOBEC activity were associated with the highest risk of postresection recurrence: SBS2 (p = 0.021) and SBS13 (p = 0.005). Three oncogenic pathways (p53, Wnt, Myc) were altered with statistical significance in MIP/SOL tumors. Compared with LEP and ACI/PAP tumors, MIP/SOL tumors had a higher frequency of targetable BRAF-V600E mutations (p = 0.046). Among ACI/PAP tumors, alterations in the cell cycle (p < 0.001) and PI3K (p = 0.002) pathways were associated with recurrence; among MIP/SOL tumors, only PI3K alterations were associated with recurrence (p = 0.049). Conclusions: These results provide the first in-depth assessment of tumor genomic profiling of predominant LUAD histologic subtypes, their associations with recurrence, and their correlation with targetable driver alterations in patients with surgically resected LUAD. © 2020 International Association for the Study of Lung Cancer |
| Keywords: | lung adenocarcinoma; histologic subtypes; next-generation sequencing; tumor genomic profiling |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 15 |
| Issue: | 12 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2020-12-01 |
| Start Page: | 1844 |
| End Page: | 1856 |
| Language: | English |
| DOI: | 10.1016/j.jtho.2020.08.005 |
| PUBMED: | 32791233 |
| PROVIDER: | scopus |
| PMCID: | PMC7704768 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 January 2021 -- Source: Scopus |
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