Establishing Novel Molecular Subtypes of Appendiceal Cancer

Autor: Mary Garland-Kledzik, Javier I. J. Orozco, Trevan D Fischer, Juan A. Santamaria-Barria, Alessio Pigazzi, Diego M. Marzese, Miquel Ensenyat-Mendez, Anthony J Scholer, Adam Khader
Rok vydání: 2021
Předmět:
Zdroj: Annals of Surgical Oncology. 29:2118-2125
ISSN: 1534-4681
1068-9265
DOI: 10.1245/s10434-021-10945-8
Popis: PURPOSE Appendiceal cancer is a rare disease process with complex treatment strategies. The objective of this study was to identify mutation-based genetic subtypes that may differ from the current histological classification, compare the genetic make-up of primaries and metastases, and find novel targetable alterations. METHODS The analyses involved the curation and normalization of gene mutation panels from appendiceal adenocarcinoma and mucinous adenocarcinoma (n = 196) stored in the AACR GENIE Database v6.0. Genes mutated in less than one patient and tumors profiled with incomplete mutation panels were excluded from the study. The optimal number of AC subtypes was established using the Nonnegative Matrix Factorization algorithm. Statistical comparisons of mutation frequencies were performed using Pearson's χ2 test. RESULTS AC patients were stratified into five mutation subtypes, based on a final set of 41 cancer-related genes. AC0 had no mutations. The most frequently mutated genes varied between the subtypes were: AC1: KRAS (91.9%) and GNAS (77.4%); AC2: KRAS (52.5%), APC (32.5%), and GNAS (30%); AC3: KMT2D (38.7%), TP53 (38.7%), KRAS (35.5%), EP300 (22.6%); and AC4: TP53 (97.2%), KRAS (77.8%), and SMAD4 (36.1%). Additionally, AC3 was less likely to be mucinous (22.6% vs. 50.0-74.2%, p
Databáze: OpenAIRE
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