Invasive Mucinous Adenocarcinomas With Spatially Separate Lung Lesions: Analysis of Clonal Relationship by Comparative Molecular Profiling.
Comparative molecular profiling
Invasive mucinous adenocarcinoma
KRAS
Lung
Molecular diagnostics
NSCLC
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
25
01
2021
revised:
18
03
2021
accepted:
22
03
2021
pubmed:
12
4
2021
medline:
10
8
2021
entrez:
11
4
2021
Statut:
ppublish
Résumé
Pulmonary invasive mucinous adenocarcinomas (IMAs) often present with spatially separate lung lesions. Clonal relationship between such lesions, particularly those involving contralateral lobes, is not well established. Here, we used comparative genomic profiling to address this question. Patients with genomic analysis performed on two IMAs located in different lung regions were identified. Molecular assays included DNA-based next-generation sequencing (NGS) for 410 to 468 genes (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets), RNA-based NGS for 62 genes (Memorial Sloan Kettering-Fusion), or non-NGS assays. Comparative genomic profiling was performed on two separate IMAs in 24 patients, of whom 19 had contralateral lesions. Tumors from all but one patient shared matching driver alterations, including KRAS (n = 19), NRG1 (n = 2), ERBB2 (n = 1) or BRAF (n = 1). In addition, in patients with paired tumors profiled by NGS (n = 12), shared driver alterations were accompanied by up to 4 (average 2.6) other identical mutations, further supporting the clonal relationship between the tumors. Only in a single patient separate IMAs harbored entirely nonoverlapping mutation profiles, supporting clonally unrelated, distinct primary tumors. Notably, in a subset of patients (n = 3), molecular testing confirmed a clonal relationship between the original resected IMAs and subsequent contralateral IMA presenting after an extremely long latency (8.1-11.7 y). Comparative molecular profiling supports that nearly all separate pulmonary IMA lesions represent intrapulmonary spread arising from a single tumor and documents a subset with a remarkably protracted course of intrapulmonary progression. This study reinforces the unique biology and clinical behavior of IMAs while further highlighting the value of genomic testing for clarifying the clonal relationship between multiple lung carcinomas.
Identifiants
pubmed: 33839364
pii: S1556-0864(21)02103-1
doi: 10.1016/j.jtho.2021.03.023
pmc: PMC8240964
mid: NIHMS1702999
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1188-1199Subventions
Organisme : NCI NIH HHS
ID : P01 CA129243
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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