학술논문
The Genomic, Transcriptomic, and Immunologic Landscape of HRAS Mutations in Solid Tumors.
Document Type
Academic Journal
Author
Kareff SA; Department of Graduate Medical Education, University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital, Miami, FL 33136, USA.; Trabolsi A; Department of Graduate Medical Education, University of Miami Sylvester Comprehensive Cancer Center/Jackson Memorial Hospital, Miami, FL 33136, USA.; Krause HB; Caris Life Sciences, Phoenix, AZ 85040, USA.; Samec T; Caris Life Sciences, Phoenix, AZ 85040, USA.; Elliott A; Caris Life Sciences, Phoenix, AZ 85040, USA.; Rodriguez E; Division of Medical Oncology, Department of Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA.; Olazagasti C; Division of Medical Oncology, Department of Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA.; Watson DC; Division of Medical Oncology, Department of Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA.; Bustos MA; Division of Translational Molecular Medicine, St. Johns' Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA.; Hoon DSB; Division of Translational Molecular Medicine, St. Johns' Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA.; Graff SL; Department of Medicine, Lifespan Cancer Institute, Providence, RI 02903, USA.; Antonarakis ES; Division of Hematology, Oncology, and Transplantation, University of Minnesota Masonic Cancer Center, Minneapolis, MN 55455, USA.; Goel S; Division of Medical Oncology, Rutgers University, New Brunswick, NJ 08901, USA.; Sledge G; Caris Life Sciences, Phoenix, AZ 85040, USA.; Lopes G; Division of Medical Oncology, Department of Medicine, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2072-6694
Abstract
Tipifarnib is the only targeted therapy breakthrough for HRAS -mutant ( HRAS mt) recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The molecular profiles of HRAS mt cancers are difficult to explore given the low frequency of HRAS mt. This study aims to understand the molecular co-alterations, immune profiles, and clinical outcomes of 524 HRAS mt solid tumors including urothelial carcinoma (UC), breast cancer (BC), non-small-cell lung cancer (NSCLC), melanoma, and HNSCC. HRAS mt was most common in UC (3.0%), followed by HNSCC (2.82%), melanoma (1.05%), BC (0.45%), and NSCLC (0.44%). HRAS mt was absent in Her2+ BC regardless of hormone receptor status. HRAS mt was more frequently associated with squamous compared to non-squamous NSCLC (60% vs. 40% in HRAS wt, p = 0.002). The tumor microenvironment (TME) of HRAS mt demonstrated increased M1 macrophages in triple-negative BC (TNBC), HNSCC, squamous NSCLC, and UC; increased M2 macrophages in TNBC; and increased CD8+ T-cells in HNSCC (all p < 0.05). Finally, HRAS mt was associated with shorter overall survival in HNSCC (HR: 1.564, CI: 1.16-2.11, p = 0.003) but not in the other cancer types examined. In conclusion, this study provides new insights into the unique molecular profiles of HRAS mt tumors that may help to identify new targets and guide future clinical trial design.