title: HIV-1 Evolutionary Patterns Associated with Metastatic Kaposi's Sarcoma during AIDS.
abstract: Kaposi's sarcoma (KS) in HIV-infected individuals can have a wide range of clinical outcomes, from indolent skin tumors to a life-threatening visceral cancer. KS tumors contain endothelial-related cells and inflammatory cells that may be HIV-infected. In this study we tested if HIV evolutionary patterns distinguish KS tumor relatedness and progression. Multisite autopsies from participants who died from HIV-AIDS with KS prior to the availability of antiretroviral therapy were identified at the AIDS and Cancer Specimen Resource (ACSR). Two patients (KS1 and KS2) died predominantly from non-KS-associated disease and KS3 died due to aggressive and metastatic KS within one month of diagnosis. Skin and visceral tumor and nontumor autopsy tissues were obtained (n = 12). Single genome sequencing was used to amplify HIV RNA and DNA, which was present in all tumors. Independent HIV tumor clades in phylogenies differentiated KS1 and KS2 from KS3, whose sequences were interrelated by both phylogeny and selection. HIV compartmentalization was confirmed in KS1 and KS2 tumors; however, in KS3, no compartmentalization was observed among sampled tissues. While the sample size is small, the HIV evolutionary patterns observed in all patients suggest an interplay between tumor cells and HIV-infected cells which provides a selective advantage and could promote KS progression.
authors.affiliation: Bioinfoexperts, LLC, 718 Bayou Lane, Thibodaux, LA 70302, USA.
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Lamers
authors.affiliation: Bioinfoexperts, LLC, 718 Bayou Lane, Thibodaux, LA 70302, USA.
authors.forename: Rebecca
authors.identifier: 0000-0002-5059-9176
authors.initials: R
authors.lastname: Rose
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Florida, 2055 Mowry Road, Gainesville, FL 32610, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nolan
authors.affiliation: Natural Selection, Inc., 5910 Pacific Center Blvd., 6480 Weathers Place, San Diego, CA 92121, USA.
authors.forename: Gary B
authors.identifier: 0000-0003-2848-3043
authors.initials: GB
authors.lastname: Fogel
authors.affiliation: Bioinfoexperts, LLC, 718 Bayou Lane, Thibodaux, LA 70302, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Barbier
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Florida, 2055 Mowry Road, Gainesville, FL 32610, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Salemi
authors.affiliation: The AIDS and Cancer Specimen Resource, University of California at San Francisco and the Department of Laboratory Medicine, Pathology, and Medicine, University of California at San Francisco, 1001 Poterero Ave, Bldg 3, Rm 207, UCSF Box 1317, San Francisco, CA 94110, USA.
authors.forename: Michael S
authors.identifier: 0000-0002-7232-2602
authors.initials: MS
authors.lastname: McGrath