Pathogenic alterations in PIK3CA and KMT2C are frequent and independent prognostic factors in anal squamous cell carcinoma treated with salvage abdominoperineal resection.
HPV associated cancer
cancer genomics
gastrointestinal cancer
genomic biomarkers
next-generation sequencing
precision medicine
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 Feb 2024
01 Feb 2024
Historique:
revised:
26
08
2023
received:
22
05
2023
accepted:
21
09
2023
pubmed:
1
11
2023
medline:
1
11
2023
entrez:
1
11
2023
Statut:
ppublish
Résumé
The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover novel prognostic biomarkers and offer potential directions for the development of targeted therapies. To that end, we assessed the prognostic and theragnostic implications of pathogenic variants identified in 571 cancer-related genes from surgical samples collected from a homogeneous, multicentric French cohort of 158 ASCC patients who underwent abdominoperineal resection treatment. Alterations in PI3K/AKT/mTOR, chromatin remodeling, and Notch pathways were frequent in HPV-positive tumors, while HPV-negative tumors often harbored variants in cell cycle regulation and genome integrity maintenance genes (e.g., frequent TP53 and TERT promoter mutations). In patients with HPV-positive tumors, KMT2C and PIK3CA exon 9/20 pathogenic variants were associated with worse overall survival in multivariate analysis (Hazard ratio (HR)
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
504-515Subventions
Organisme : Fondation de France
Organisme : Ligue Contre le Cancer
Organisme : Société Nationale Française de Gastroentérologie
Informations de copyright
© 2023 UICC.
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