Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin

被引：59

作者：

Rodriguez-Paredes, Manuel ^{[1
]}

Bormann, Felix ^{[1
]}

Raddatz, Guenter ^{[1
]}

Gutekunst, Julian ^{[1
]}

Lucena-Porcel, Carlota ^{[2
,3
]}

Koehler, Florian ^{[1
]}

Wurzer, Elisabeth ^{[4
]}

Schmidt, Katrin ^{[4
]}

Gallinat, Stefan ^{[4
]}

Wenck, Horst ^{[4
]}

Roewert-Huber, Joachim ^{[5
]}

Denisova, Evgeniya ^{[6
]}

Feuerbach, Lars ^{[6
]}

Park, Jeongbin ^{[7
]}

Brors, Benedikt ^{[6
,8
,9
]}

Herpel, Esther ^{[2
,3
]}

Nindl, Ingo ^{[5
]}

Hofmann, Thomas G. ^{[1
]}

Winnefeld, Marc ^{[4
]}

Lyko, Frank ^{[1
]}

机构：

[1] German Canc Res Ctr, Div Epigenet, DKFZ ZMBH Alliance, D-69120 Heidelberg, Germany

[2] Heidelberg Univ, Inst Pathol, D-69120 Heidelberg, Germany

[3] Natl Ctr Tumor Dis NCT, Tissue Bank, D-69120 Heidelberg, Germany

[4] Beiersdorf AG, Res & Dev, D-20253 Hamburg, Germany

[5] Univ Hosp, Charite, Dept Dermatol Venereol & Allergy, D-10117 Berlin, Germany

[6] German Canc Res Ctr, Div Appl Bioinformat, D-69120 Heidelberg, Germany

[7] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany

[8] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany

[9] German Canc Res Ctr, German Canc Consortium DKTK, D-69120 Heidelberg, Germany

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

GENE NUMERICAL ABERRATIONS; ACTINIC KERATOSIS; DNA METHYLATION; TUMOR-SUPPRESSOR; STEM-CELLS; EXPRESSION; CANCER; SKIN; P63; P53;

D O I：

10.1038/s41467-018-03025-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and usually progresses from a UV-induced precancerous lesion termed actinic keratosis (AK). Despite various efforts to characterize these lesions molecularly, the etiology of AK and its progression to cSCC remain partially understood. Here, we use Infinium MethylationEPIC BeadChips to interrogate the DNA methylation status in healthy, AK and cSCC epidermis samples. Importantly, we show that AK methylation patterns already display classical features of cancer methylomes and are highly similar to cSCC profiles. Further analysis identifies typical features of stem cell methylomes, such as reduced DNA methylation age, non-CpG methylation, and stem cell-related keratin and enhancer methylation patterns. Interestingly, this signature is detected only in half of the samples, while the other half shows patterns more closely related to healthy epidermis. These findings suggest the existence of two subclasses of AK and cSCC emerging from distinct keratinocyte differentiation stages.

引用

页数：9

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