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@ARTICLE{Leiendecker:186717,
author = {L. Leiendecker and T. Neumann and P. S. Jung and S. M.
Cronin and T. L. Steinacker and A. Schleiffer and M.
Schutzbier and K. Mechtler and T. Kervarrec and E. Laurent
and K. Bachiri and E. Coyaud and R. Murali and K. J. Busam
and B. Itzinger-Monshi and R. Kirnbauer and L. Cerroni and
E. Calonje and A. Rütten and F. Stubenrauch and K. G.
Griewank$^*$ and T. Wiesner and A. C. Obenauf},
title = {{H}uman {P}apillomavirus 42 {D}rives {D}igital {P}apillary
{A}denocarcinoma and {E}licits a {G}erm {C}ell-like
{P}rogram {C}onserved in {HPV}-{P}ositive {C}ancers.},
journal = {Cancer discovery},
volume = {13},
number = {1},
issn = {2159-8274},
address = {Philadelphia, Pa.},
reportid = {DKFZ-2023-00074},
pages = {70 - 84},
year = {2023},
abstract = {The 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.},
keywords = {Female / Humans / Human Papillomavirus Viruses /
Papillomavirus Infections: complications / Uterine Cervical
Neoplasms / Skin Neoplasms / Bone Neoplasms / Breast
Neoplasms / Papillomaviridae: genetics / Adenocarcinoma,
Clear Cell / Adenocarcinoma, Papillary / Germ Cells:
pathology},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36213965},
pmc = {pmc:PMC9827110},
doi = {10.1158/2159-8290.CD-22-0489},
url = {https://inrepo02.dkfz.de/record/186717},
}