Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved..
RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(-) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(-) cases are required to understand this important LUAD subset.
| Errataetall: |
ErratumIn: Cell Rep. 2021 Feb 23;34(8):108784. - PMID 33626341 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
Cell reports - 34(2021), 5 vom: 02. Feb., Seite 108707 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Carrot-Zhang, Jian [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.02.2022 Date Revised 07.05.2022 published: Print ErratumIn: Cell Rep. 2021 Feb 23;34(8):108784. - PMID 33626341 Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2021.108707 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM320957950 |
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| 500 | |a ErratumIn: Cell Rep. 2021 Feb 23;34(8):108784. - PMID 33626341 | ||
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| 520 | |a Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(-) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(-) cases are required to understand this important LUAD subset | ||
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| 650 | 4 | |a genome analysis | |
| 650 | 4 | |a lung adenocarcinoma | |
| 650 | 4 | |a noncoding | |
| 650 | 4 | |a oncogene | |
| 650 | 4 | |a precision oncology | |
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