Carolina Caro-Vegas1,2, Catalina Ramirez1,3, Justin Landis1,2, Adaora A Adimora1,3, Howard Strickler4, Audrey L French5, Igho Ofotokun6, Margaret Fischl7, Eric C Seaberg8, Chia-Ching J Wang9, Amanda B Spence10, Dirk P Dittmer1,2. 1. UNC Lineberger Comprehensive Cancer Center and Center for AIDS Research. 2. UNC Department of Microbiology and Immunology. 3. UNC Department of Medicine Division of Infectious Diseases, Chapel Hill, North Carolina. 4. Albert Einstein College of Medicine, Department of Epidemiology, Bronx, New York. 5. Stronger Hospital of Cook County Health, Division of Infectious Diseases Chicago, Illinois. 6. Emory University School of Medicine, Division of Infectious Diseases, Atlanta, Georgia. 7. University of Miami Department of Medicine, Division of Infectious Diseases, Miami, Florida. 8. Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, Maryland. 9. UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California. 10. Georgetown University Medical Center, Division of Infectious Diseases, Washington, District of Columbia, USA.
Abstract
OBJECTIVE: This 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). DESIGN: Previous 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. METHODS: The 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. RESULTS: There 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). CONCLUSION: This 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.
OBJECTIVE: This 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). DESIGN: Previous 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. METHODS: The 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. RESULTS: There 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). CONCLUSION: This 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.
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Authors: Thomas S Uldrick; Priscila H Gonçalves; Maher Abdul-Hay; Alisa J Claeys; Brinda Emu; Marc S Ernstoff; Steven P Fling; Lawrence Fong; Judith C Kaiser; Andreanne M Lacroix; Steve Y Lee; Lisa M Lundgren; Kathryn Lurain; Christopher H Parsons; Sharavi Peeramsetti; Ramya Ramaswami; Elad Sharon; Mario Sznol; Chia-Ching Jackie Wang; Robert Yarchoan; Martin A Cheever Journal: JAMA Oncol Date: 2019-09-01 Impact factor: 31.777
Authors: Adaora A Adimora; Catalina Ramirez; Lorie Benning; Ruth M Greenblatt; Mirjam-Colette Kempf; Phyllis C Tien; Seble G Kassaye; Kathryn Anastos; Mardge Cohen; Howard Minkoff; Gina Wingood; Igho Ofotokun; Margaret A Fischl; Stephen Gange Journal: Int J Epidemiol Date: 2018-04-01 Impact factor: 7.196
Authors: L Dal Maso; S Franceschi; J Polesel; C Braga; P Piselli; E Crocetti; F Falcini; S Guzzinati; R Zanetti; M Vercelli; G Rezza Journal: Br J Cancer Date: 2003-07-07 Impact factor: 7.640