Genomic Alterations in the RB Pathway Indicate Prognostic Outcomes of Early-Stage Lung Adenocarcinoma

Mené sur des échantillons tumoraux prélevés sur 247 patients atteints d'un adénocarcinome du poumon, cette étude met notamment en évidence une association entre la présence d'anomalies génomiques dans la voie de signalisation RB et un pronostic défavorable pour les patients atteints d'un cancer de stade précoce

Résumé en anglais

Purpose: To better understand the complete genomic architecture of lung adenocarcinoma (LA).

Experimental Design: We used array experiments to determine copy number variations and sequenced the complete exomes of the 247 LA tumor samples along with matched normal cells obtained from the same patients. Fully annotated clinical data were also available, providing an unprecedented opportunity to assess the impact of genomic alterations on clinical outcomes.

Results: We discovered that genomic alternations in the RB pathway are associated with significantly shorter disease-free survival in early-stage LA patients. This association was also observed in our independent validation cohort. The current treatment guidelines for early-stage LA patients recommend follow-up without adjuvant therapy after complete resection, except for high-risk patients. However, our findings raise the interesting possibility that additional clinical interventions might provide medical benefits to early-stage LA patients with genomic alterations in the RB pathway. When examining the association between genomic mutation and histological subtype, we uncovered the characteristic genomic signatures of various histological subtypes. Notably, the solid and the micropapillary subtypes demonstrated great diversity in the mutated genes, while the mucinous subtype exhibited the most unique landscape. This suggests that a more tailored therapeutic approach should be used to treat LA patients.

Conclusion: Our analysis of the genomic and clinical data for 247 LAs should help provide a more comprehensive genomic portrait of LA, define molecular signatures of LA subtypes, and lead to the discovery of useful prognostic markers that could be used in personalized treatments for early-stage LA patients.