Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability

被引：53

作者：

Jaekel, Cornelia ^{[1
]}

Bergmann, Frank ^{[2
]}

Toth, Reka ^{[1
]}

Assenov, Yassen ^{[1
]}

van der Duin, Daniel ^{[1
]}

Strobel, Oliver ^{[3
]}

Hank, Thomas ^{[3
]}

Kloeppel, Guenter ^{[4
]}

Dorrell, Craig ^{[5
]}

Grompe, Markus ^{[5
]}

Moss, Joshua ^{[6
]}

Dor, Yuval ^{[6
]}

Schirmacher, Peter ^{[2
]}

Plass, Christoph ^{[1
]}

Popanda, Odilia ^{[1
]}

Schmezer, Peter ^{[1
]}

机构：

[1] German Canc Res Ctr, Div Epigen & Canc Risk Factors, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[2] Univ Hosp Heidelberg, Inst Pathol, Neuenheimer Feld 224, D-69120 Heidelberg, Germany

[3] Univ Hosp Heidelberg, Dept Gen & Visceral Surg, Neuenheimer Feld 110, D-69120 Heidelberg, Germany

[4] Tech Univ Munich, Inst Pathol, Trogerstr 18, D-81675 Munich, Germany

[5] Oregon Hlth & Sci Univ, Dept Pediat, Pape Family Pediat Res Inst, Oregon Stem Cell Ctr, Portland, OR 97239 USA

[6] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Dev Biol & Canc Res, Inst Med Res Israel Canada, IL-9112102 Jerusalem, Israel

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

DNA METHYLATION; MUTATIONAL SIGNATURES; TRANSCRIPTION FACTOR; CANCER-CELLS; CYCLIN D1; TUMORS; EXPRESSION; PATTERNS; ARID1A; HETEROGENEITY;

D O I：

10.1038/s41467-017-01118-x

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：

Pancreatic acinar cell carcinoma (ACC) is an aggressive exocrine tumor with largely unknown biology. Here, to identify potential targets for personalized treatment, we perform integrative genome-wide and epigenome-wide analyses. The results show frequently aberrant DNA methylation, abundant chromosomal amplifications and deletions, and mutational signatures suggesting defective DNA repair. In contrast to pancreatic ductal adenocarcinoma, no recurrent point mutations are detected. The tumor suppressors ID3, ARID1A, APC, and CDKN2A are frequently impaired also on the protein level and thus potentially affect ACC tumorigenesis. Consequently, this work identifies promising therapeutic targets in ACC for drugs recently approved for precision cancer therapy.

引用

页数：10

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