1. Molecular profiling of breast and lung cancer in women with HIV reveals high tumor mutational burden
- Author
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Caro-Vegas, Carolina, Ramirez, Catalina, Landis, Justin, Adimora, Adaora A, Strickler, Howard, French, Audrey L, Ofotokun, Igho, Fischl, Margaret, Seaberg, Eric C, Wang, Chia-Ching J, Spence, Amanda B, and Dittmer, Dirk P
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Breast Cancer ,Lung Cancer ,HIV/AIDS ,Genetics ,Human Genome ,Clinical Research ,Lung ,Good Health and Well Being ,Biomarkers ,Tumor ,Female ,HIV Infections ,High-Throughput Nucleotide Sequencing ,Humans ,Lung Neoplasms ,Mutation ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveThis study compared the mutation profile and tumor mutational burden (TMB) in women with HIV (WWH) diagnosed with lung adenocarcinoma (n = 8) or breast ductal neoplasm (n = 13) who were enrolled into the Women's Interagency HIV Study (WIHS).DesignPrevious studies tended to focus on single institutions based on sample availability. This study is based on a representative, multicenter cohort that represents the racial and ethnic composition of women with HIV in the United States.MethodsThe study sequenced the complete human exome of n = 26 cancer samples from HIV-positive women, using Ion torrent next-generation sequencing. The study cohort was compared with a HIV-negative cohort obtained from the Genomic Data Commons Data Portal of the NCI.ResultsThere were no differences in known cancer mutations between breast cancer and lung cancer that developed in WWH and those that developed in HIV-negative (HIV-) women; however, WWH presented a significantly higher TMB in comparison to HIV- patients. Seventy-five percent of lung cancers and 61% of breast cancers were defined as TMB-high (more than 10 mutation/mb of DNA).ConclusionThis study affirms the recommendation that WWH be included in clinical trials of novel treatments for these cancers. Although these data are preliminary, the high TMB in WLHV suggests, paradoxically, that this immune challenged population may benefit greatly from immune checkpoint inhibitor therapies.
- Published
- 2022