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. 2022 Oct 10;13(1):70–84. doi: 10.1158/2159-8290.CD-22-0489

Figure 1.

Figure 1. HPV42 is associated with DPA. A, Overview of unbiased screening approach for detection of vertebrate-infecting viruses in targeted next-generation sequencing (NGS) data. Targeted NGS data from 18 skin tumor types and Merkel cell carcinoma (MCC, positive control) were analyzed with the centrifuge metagenomic classifier utilizing a custom viral database (Viral DB). B, Virus abundance score in targeted NGS data of 214 human tumor samples. Detection of HPV42 in 100% (n = 11/11) of DPA samples. DPA, digital papillary adenocarcinoma; MCC, Merkel cell carcinoma; LM, lentigo maligna melanoma; PM, pediatric melanoma; PPT, proliferating pilar cystic tumor; ACC, adenoid cystic carcinoma; AFX, atypical fibroxanthoma; AS, angiosarcoma; BPDCN, blastic plasmacytoid dendritic cell neoplasm; DM, desmoplastic melanoma; DTE, desmoplastic trichoepithelioma; EPC, eccrine porocarcinoma; ES, eccrine spiradenoma; MAC, microcystic adnexal carcinoma; poroma, poroma; SAC, spiradenocarcinoma; SC, sebaceous carcinoma; SGC, sweat gland carcinoma; SKCM, cutaneous melanoma. Viral prevalence: proportion of samples with detected virus in any given tumor type. Abundance score: mean proportion of detected virus in any given tumor type. C, HPV42 abundance score in a cohort of 17 DPAs after sequence capture to DNA and RNA of 6,453 viruses. White diamond: HPV42 detected but below an abundance of 1%. ND: not determined. D, Top, Circos plot depicting HPV42-human genome breakpoints. Each arch represents one detected breakpoint. Bottom, lollipop presentation of integration breakpoints in the HPV42 genome. Each lollipop represents one breakpoint (Supplementary Table S4). E, FISH signal of HPV42 genome (magenta) and human genome integration site adjacent locus (yellow) in DPA nuclei (blue). White arrows indicate fusion signals. Scale bar, 2.5 μm. Individual channels and quantifications in Supplementary Fig. S4. F, (Top), RNA in situ hybridization (ISH) staining for expression of early region HPV42 mRNA in lung metastasis of a DPA tumor (T) and the surrounding normal (N) tissue. Scale bar, 1 mm; (bottom) Inset. Scale bar, 20 μm.

HPV42 is associated with DPA. A, Overview of unbiased screening approach for detection of vertebrate-infecting viruses in targeted next-generation sequencing (NGS) data. Targeted NGS data from 18 skin tumor types and MCC (positive control, pos. ctrl.) were analyzed with the centrifuge metagenomic classifier utilizing a custom viral database (Viral DB). B, Virus abundance score in targeted NGS data of 214 human tumor samples. Detection of HPV42 in 100% (n = 11/11) of DPA samples. ACC, adenoid cystic carcinoma; AFX, atypical fibroxanthoma; AS, angiosarcoma; BPDCN, blastic plasmacytoid dendritic cell neoplasm; DM, desmoplastic melanoma; DTE, desmoplastic trichoepithelioma; EPC, eccrine porocarcinoma; ES, eccrine spiradenoma; LM, lentigo maligna melanoma; MAC, microcystic adnexal carcinoma; PM, pediatric melanoma; PPT, proliferating pilar cystic tumor; SAC, spiradenocarcinoma; SC, sebaceous carcinoma; SGC, sweat gland carcinoma; SKCM, cutaneous melanoma. Viral prevalence: proportion of samples with detected virus in any given tumor type. Abundance score: mean proportion of detected virus in any given tumor type. C, HPV42 abundance score in a cohort of 17 DPAs after sequence capture to DNA and RNA of 6,453 viruses. White diamond: HPV42 detected but below an abundance of 1%. ND, not determined. D, Top, Circos plot depicting HPV42–human genome breakpoints. Each arch represents one detected breakpoint. Bottom, lollipop presentation of integration breakpoints in the HPV42 genome. Each lollipop represents one breakpoint (Supplementary Table S4). E, FISH signal of HPV42 genome (magenta) and human genome integration site adjacent locus (yellow) in DPA nuclei (blue). White arrowheads indicate fusion signals. Scale bar, 2.5 μm. Individual channels and quantifications in Supplementary Fig. S4. F, Top, RNA-ISH staining for expression of early region HPV42 mRNA in lung metastasis of a DPA tumor (T) and the surrounding normal (N) tissue. Scale bar, 1 mm. Bottom, inset. Scale bar, 20 μm.