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000186717 1001_ $$00000-0002-6164-3953$$aLeiendecker, Lukas$$b0
000186717 245__ $$aHuman Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell-like Program Conserved in HPV-Positive Cancers.
000186717 260__ $$aPhiladelphia, Pa.$$c2023
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000186717 520__ $$aThe skin is exposed to viral pathogens, but whether they contribute to the oncogenesis of skin cancers has not been systematically explored. Here we investigated 19 skin tumor types by analyzing off-target reads from commonly available next-generation sequencing data for viral pathogens. We identified human papillomavirus 42 (HPV42) in 96% (n = 45/47) of digital papillary adenocarcinoma (DPA), an aggressive cancer occurring on the fingers and toes. We show that HPV42, so far considered a nononcogenic, 'low-risk' HPV, recapitulates the molecular hallmarks of oncogenic, 'high-risk' HPVs. Using machine learning, we find that HPV-driven transformation elicits a germ cell-like transcriptional program conserved throughout all HPV-driven cancers (DPA, cervical carcinoma, and head and neck cancer). We further show that this germ cell-like transcriptional program, even when reduced to the top two genes (CDKN2A and SYCP2), serves as a fingerprint of oncogenic HPVs with implications for early detection, diagnosis, and therapy of all HPV-driven cancers.We identify HPV42 as a uniform driver of DPA and add a new member to the short list of tumorigenic viruses in humans. We discover that all oncogenic HPVs evoke a germ cell-like transcriptional program with important implications for detecting, diagnosing, and treating all HPV-driven cancers. See related commentary by Starrett et al., p. 17. This article is highlighted in the In This Issue feature, p. 1.
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000186717 650_2 $$2MeSH$$aFemale
000186717 650_2 $$2MeSH$$aHumans
000186717 650_2 $$2MeSH$$aHuman Papillomavirus Viruses
000186717 650_2 $$2MeSH$$aPapillomavirus Infections: complications
000186717 650_2 $$2MeSH$$aUterine Cervical Neoplasms
000186717 650_2 $$2MeSH$$aSkin Neoplasms
000186717 650_2 $$2MeSH$$aBone Neoplasms
000186717 650_2 $$2MeSH$$aBreast Neoplasms
000186717 650_2 $$2MeSH$$aPapillomaviridae: genetics
000186717 650_2 $$2MeSH$$aAdenocarcinoma, Clear Cell
000186717 650_2 $$2MeSH$$aAdenocarcinoma, Papillary
000186717 650_2 $$2MeSH$$aGerm Cells: pathology
000186717 7001_ $$00000-0003-3908-4224$$aNeumann, Tobias$$b1
000186717 7001_ $$00000-0002-8864-4091$$aJung, Pauline S$$b2
000186717 7001_ $$00000-0003-3602-7160$$aCronin, Shona M$$b3
000186717 7001_ $$00000-0002-7244-5610$$aSteinacker, Thomas L$$b4
000186717 7001_ $$00000-0001-6251-2747$$aSchleiffer, Alexander$$b5
000186717 7001_ $$00000-0003-4856-262X$$aSchutzbier, Michael$$b6
000186717 7001_ $$00000-0002-3392-9946$$aMechtler, Karl$$b7
000186717 7001_ $$00000-0002-2201-6914$$aKervarrec, Thibault$$b8
000186717 7001_ $$00000-0002-6138-2992$$aLaurent, Estelle$$b9
000186717 7001_ $$00000-0003-0297-0521$$aBachiri, Kamel$$b10
000186717 7001_ $$00000-0002-5893-4557$$aCoyaud, Etienne$$b11
000186717 7001_ $$00000-0001-6988-4295$$aMurali, Rajmohan$$b12
000186717 7001_ $$00000-0003-0888-9601$$aBusam, Klaus J$$b13
000186717 7001_ $$00000-0002-2988-2380$$aItzinger-Monshi, Babak$$b14
000186717 7001_ $$00000-0002-5588-4179$$aKirnbauer, Reinhard$$b15
000186717 7001_ $$00000-0003-4986-9113$$aCerroni, Lorenzo$$b16
000186717 7001_ $$00000-0001-7475-6423$$aCalonje, Eduardo$$b17
000186717 7001_ $$00000-0001-5718-331X$$aRütten, Arno$$b18
000186717 7001_ $$00000-0002-6685-299X$$aStubenrauch, Frank$$b19
000186717 7001_ $$00000-0003-3899-9449$$aGriewank, Klaus G$$b20
000186717 7001_ $$00000-0001-5877-2992$$aWiesner, Thomas$$b21
000186717 7001_ $$00000-0002-9556-5914$$aObenauf, Anna C$$b22
000186717 773__ $$0PERI:(DE-600)2607892-2$$a10.1158/2159-8290.CD-22-0489$$gVol. 13, no. 1, p. 70 - 84$$n1$$p70 - 84$$tCancer discovery$$v13$$x2159-8274$$y2023
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