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Diagnosis and Treatment of Kaposi Sarcoma.

ABSTRACT: Kaposi sarcoma (KS) is the most common neoplasm of people living with HIV today. In Sub-Saharan Africa, KS is among the most common cancers in men, overall. Not only HIV-positive individuals present with KS; any immune compromised person infected with KS-associated herpesvirus (KSHV) or human herpesvirus 8 is at risk: the elderly, children in KSHV-endemic areas, and transplant recipients. KS diagnosis is based on detection of the viral protein latency-associated nuclear antigen (LANA) in the biopsy, but not all cases of KS are the same or will respond to the same therapy. Standard KS therapy has not changed in 20 years, but newer modalities are on the horizon and will be discussed.

SUBMITTER: Schneider JW

PROVIDER: S-EPMC5509489 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Diagnosis and Treatment of Kaposi Sarcoma.

Schneider Johann W JW Dittmer Dirk P DP

American journal of clinical dermatology 20170801 4

Kaposi sarcoma (KS) is the most common neoplasm of people living with HIV today. In Sub-Saharan Africa, KS is among the most common cancers in men, overall. Not only HIV-positive individuals present with KS; any immune compromised person infected with KS-associated herpesvirus (KSHV) or human herpesvirus 8 is at risk: the elderly, children in KSHV-endemic areas, and transplant recipients. KS diagnosis is based on detection of the viral protein latency-associated nuclear antigen (LANA) in the bio ...[more]

PMID: 28324233

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Project description:Intra-host tumor virus variants may influence the pathogenesis and treatment responses of some virally-associated cancers. However, the intra-host variability of Kaposi sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi sarcoma (KS), has to date been explored with sequencing technologies that possibly introduce more errors than that which occurs in the viral population, and these studies have only studied variable regions. Here, full-length KSHV genomes in tumors and/or oral swabs from 9 Ugandan adults with HIV-associated KS were characterized. Furthermore, we used deep, short-read sequencing using duplex unique molecular identifiers (dUMI)-random double-stranded oligonucleotides that barcode individual DNA molecules before library amplification. This allowed suppression of PCR and sequencing errors to ~10-9/base as well as afforded accurate determination of KSHV genome numbers sequenced in each sample. KSHV genomes were assembled de novo, and rearrangements observed were confirmed by PCR and Sanger sequencing. 131-kb KSHV genome sequences, excluding major repeat regions, were successfully obtained from 23 clinical specimens, averaging 2.3x104 reads/base. Strikingly, KSHV genomes were virtually identical within individuals at the point mutational level. The intra-host heterogeneity that was observed was confined to tumor-associated KSHV mutations and genome rearrangements, all impacting protein-coding sequences. Although it is unclear whether these changes were important to tumorigenesis or occurred as a result of genomic instability in tumors, similar changes were observed across individuals. These included inactivation of the K8.1 gene in tumors of 3 individuals and retention of a region around the first major internal repeat (IR1) in all instances of genomic deletions and rearrangements. Notably, the same breakpoint junctions were found in distinct tumors within single individuals, suggesting metastatic spread of rearranged KSHV genomes. These findings define KSHV intra-host heterogeneity in vivo with greater precision than has been possible in the past and suggest the possibility that aberrant KSHV genomes may contribute to aspects of KS tumorigenesis. Furthermore, study of KSHV with use of dUMI provides a proof of concept for utilizing this technique for detailed study of other virus populations in vivo.

Dataset Information

Diagnosis and Treatment of Kaposi Sarcoma.

Publications

Diagnosis and Treatment of Kaposi Sarcoma.

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