Landscape of Concomitant Driver Alterations in Classical EGFR-Mutated Non-Small Cell Lung Cancer.
JCO Precis Oncol
; 8: e2300520, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-39102631
ABSTRACT
PURPOSE:
Next-generation sequencing (NGS) has enabled the detection of concomitant driver alterations in non-small cell lung cancer (NSCLC). However, the magnitude and clinical relevance of concomitant drivers remain to be explored.METHODS:
We profiled concomitant driver alterations of EGFR+ NSCLC by using targeted NGS. The associated genomic and clinical features were analyzed and validated in an independent The Cancer Genome Atlas cohort of patients with EGFR+ NSCLC.RESULTS:
Out of the total patient population, 334 patients had EGFR mutations along with concomitant driver mutations, comprising 3.09% of the entire cohort. The most frequent co-occurring mutations with sensitizing EGFR mutations include KRAS at 53.9%, followed by ERBB2 at 24.3%, MET at 16.5%, and BRAF at 3.3%. KRAS mutations in concomitant drivers were frequently hyperexchange mutations (25.6% v 8.2%, P < .001), compared with KRAS single drivers. EGFR/ERBB2 drivers exhibited a higher incidence of ERBB2 amplification (40.7% v 16.5%, P < .001) and p.S310F/Y mutations (44.4% v 4.3%, P < .001) compared with ERBB2 alone. EGFR/MET drivers had a higher frequency of MET amplification (71.4% v 43.3%) than MET single drivers. At the genomic level, the median number of additional concurrent mutations was four, with TSC2 (4%), CD274 (1%), and TP53 (63%) being the most frequently coaltered genes in concomitant driver tumors. Interestingly, clonality analysis indicated that EGFR mutations were more likely to occur as clonal events, whereas the codrivers were more often subclonal. Patients with concomitant drivers or with concomitant MET amplification exhibited worse prognosis.CONCLUSION:
These findings might aid in the selection of effective therapeutic regimens and facilitate the development of combination therapies.
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
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Receptores ErbB
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Neoplasias Pulmonares
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Mutación
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
JCO Precis Oncol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China