Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2018 Sep 11;115(37):E8580-E8582.
doi: 10.1073/pnas.1803292115. Epub 2018 Sep 4.

Hypomethylation, endogenous retrovirus expression, and interferon signaling in testicular germ cell tumors

Affiliations
Comment

Hypomethylation, endogenous retrovirus expression, and interferon signaling in testicular germ cell tumors

Michael C Haffner et al. Proc Natl Acad Sci U S A. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement: C.G.D. has served as a paid consultant to Roche Genentech, Merck, and Novartis, and has received sponsored research funding from the Bristol-Myers Squibb International Immuno-Oncology Network and from Janssen, Inc. A.M.D.M. has received sponsored research funding from Janssen, Inc.

Figures

Fig. 1.
Fig. 1.
(A) Micrographs of TGCTs immunolabeled for 5-methyl-cytosine (5mC) in which seminoma cells (arrowheads) and intratumoral lymphocytes (arrows) are shown. Ca, carcinoma(s). (B) Global 5mC levels in 22 seminomas, 14 embryonal Ca, 11 yolk sac tumors, and 9 teratomas. (C) CD8+ T cells in TGCTs. HPF, high-power field. (D and E) Expression of HERV-Fc1, HERV-W1 seminoma (n = 9), embryonal Ca (n = 7), and teratoma (n = 3), as well as benign testis (n = 3). (F) In situ detection of HERV-Fc1 is restricted to neoplastic seminoma cells (arrowheads) and not present in adjacent benign cells (arrows). (G) Top up-regulated gene sets in seminoma vs. nonseminomatous TGCTs. (H) IFNA1 expression in seminoma (S) and nonseminomatous TGCT (NS). (I) IFNA1 expression in tumor-associated inflammatory cells (IC) and neoplastic cells (NC) isolated by laser capture microdissection (LCM) of seminoma tissues. (JL) Expression of IFN/viral response-related genes. Strong immunoreactivity for IFIT1 and MX1 is present in neoplastic cells (arrowheads) in seminoma, and focal reactivity is present in stromal cells and a subset of tumor-associated lymphocytes (arrows). (Scale bars: 100 μm.)

Comment in

  • Reply to Haffner et al.: DNA hypomethylation renders tumors more immunogenic.
    Stone ML, Chiappinelli KB, Li H, Murphy LM, Travers ME, Topper MJ, Mathios D, Lim M, Shih IM, Wang TL, Hung CF, Bhargava V, Wiehagen KR, Cowley GS, Bachman KE, Strick R, Strissel PL, Baylin SB, Zahnow CA. Stone ML, et al. Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):E8583-E8584. doi: 10.1073/pnas.1811015115. Epub 2018 Sep 4. Proc Natl Acad Sci U S A. 2018. PMID: 30181297 Free PMC article. No abstract available.

Comment on

References

    1. Baylin SB, Jones PA. A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 2011;11:726–734. - PMC - PubMed
    1. Stone ML, et al. Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden. Proc Natl Acad Sci USA. 2017;114:E10981–E10990. - PMC - PubMed
    1. Chiappinelli KB, et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell. 2015;162:974–986. - PMC - PubMed
    1. Roulois D, et al. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell. 2015;162:961–973. - PMC - PubMed
    1. Peltomäki P. DNA methylation changes in human testicular cancer. Biochim Biophys Acta. 1991;1096:187–196. - PubMed

Supplementary concepts

LinkOut - more resources