Genomic analyses of gynaecologic carcinosarcomas reveal frequent mutations in chromatin remodelling genes

被引：136

作者：

Jones, Sian ^{[1
]}

Stransky, Nicolas ^{[2
]}

McCord, Christine L. ^{[1
]}

Cerami, Ethan ^{[2
]}

Lagowski, James ^{[3
]}

Kelly, Devon ^{[3
]}

Angiuoli, Samuel V. ^{[1
]}

Sausen, Mark ^{[1
]}

Kann, Lisa ^{[1
]}

Shukla, Manish ^{[1
]}

Makar, Rosemary ^{[3
]}

Wood, Laura D. ^{[4
]}

Diaz, Luis A., Jr. ^{[5
,6
,7
]}

Lengauer, Christoph ^{[2
]}

Velculescu, Victor E. ^{[5
]}

机构：

[1] Personal Genome Diagnost, Baltimore, MD 21224 USA

[2] Blueprint Med, Cambridge, MA 02142 USA

[3] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA

[4] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21287 USA

[5] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA

[6] Swim Amer Lab, Baltimore, MD 21287 USA

[7] Ludwig Ctr Canc Genet & Therapeut Johns Hopkins, Baltimore, MD 21287 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

MIXED MULLERIAN TUMORS; SOMATIC MUTATIONS; UBIQUITIN LIGASE; SUPPRESSOR; CARCINOMA; PATTERNS; LANDSCAPE; UTERUS; ARID1A; OVARY;

D O I：

10.1038/ncomms6006

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：

Malignant mixed Mullerian tumours, also known as carcinosarcomas, are rare tumours of gynaecological origin. Here we perform whole-exome analyses of 22 tumours using massively parallel sequencing to determine the mutational landscape of this tumour type. On average, we identify 43 mutations per tumour, excluding four cases with a mutator phenotype that harboured inactivating mutations in mismatch repair genes. In addition to mutations in TP53 and KRAS, we identify genetic alterations in chromatin remodelling genes, ARID1A and ARID1B, in histone methyltransferase MLL3, in histone deacetylase modifier SPOP and in chromatin assembly factor BAZ1A, in nearly two thirds of cases. Alterations in genes with potential clinical utility are observed in more than three quarters of the cases and included members of the PI3-kinase and homologous DNA repair pathways. These findings highlight the importance of the dysregulation of chromatin remodelling in carcinosarcoma tumorigenesis and suggest new avenues for personalized therapy.

引用

页数：7

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