Frequent amplification of receptor tyrosine kinase genes in well-differentiated/dedifferentiated liposarcoma

被引：37

作者：

Asano, Naofumi ^{[1
,2
]}

Yoshida, Akihiko ^{[3
,4
]}

Mitani, Sachiyo ^{[5
]}

Kobayashi, Eisuke

Shiotani, Bunsyo ^{[7
]}

Komiyama, Motokiyo ^{[8
]}

Fujimoto, Hiroyuki ^{[8
]}

Chuman, Hirokazu ^{[6
]}

Morioka, Hideo ^{[2
]}

Matsumoto, Morio ^{[2
]}

Nakamura, Masaya ^{[2
]}

Kubo, Takashi ^{[9
]}

Kato, Mamoru ^{[10
]}

Kohno, Takashi ^{[9
,11
]}

Kawai, Akira ^{[6
]}

Kondo, Tadashi ^{[1
]}

Ichikawa, Hitoshi ^{[5
,9
]}

机构：

[1] Natl Canc Ctr, Div Rare Canc Res, Res Inst, Chuo Ku, Tokyo 1040045, Japan

[2] Keio Univ, Sch Med, Dept Orthopaed Surg, Shinjuku Ku, Tokyo 1608582, Japan

[3] Natl Canc Ctr, Dept Pathol, Chuo Ku, Tokyo 1040045, Japan

[4] Natl Canc Ctr, Clin Lab, Chuo Ku, Tokyo 1040045, Japan

[5] Natl Canc Ctr, Dept Clin Genom, Res Inst, Chuo Ku, Tokyo 1040045, Japan

[6] Natl Canc Ctr, Dept Musculoskeletal Oncol, Chuo Ku, Tokyo 1040045, Japan

[7] Natl Canc Ctr, Div Genet, Res Inst, Chuo Ku, Tokyo 1040045, Japan

[8] Natl Canc Ctr, Dept Urol, Chuo Ku, Tokyo 1040045, Japan

[9] Natl Canc Ctr, Div Translat Genom, Exploratory Oncol Res & Clin Trial Ctr, Chuo Ku, Tokyo 1040045, Japan

[10] Natl Canc Ctr, Dept Bioinformat, Res Inst, Chuo Ku, Tokyo 1040045, Japan

[11] Natl Canc Ctr, Res Inst, Div Genome Biol, Chuo Ku, Tokyo 1040045, Japan

来源：

ONCOTARGET | 2017年 / 8卷 / 08期

关键词：

liposarcoma; well-differentiated liposarcoma; dedifferentiated liposarcoma; next-generation sequencing; receptor tyrosine kinase; SOFT-TISSUE SARCOMA; DEDIFFERENTIATED LIPOSARCOMA; PHASE-II; CANCER GENOMICS; ADIPOCYTIC DIFFERENTIATION; TUMOR SAMPLES; TRIAL; INHIBITOR; PAZOPANIB; CDK4;

D O I：

10.18632/oncotarget.14652

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are closely related tumors commonly characterized by MDM2/CDK4 gene amplification, and lack clinically effective treatment options when inoperable. To identify novel therapeutic targets, we performed targeted genomic sequencing analysis of 19 WDLPS and 37 DDLPS tumor samples using a panel of 104 cancer-related genes (NCC oncopanel v3) developed specifically for genomic testing to select suitable molecular targeted therapies. The results of this analysis indicated that these sarcomas had very few gene mutations and a high frequency of amplifications of not only MDM2 and CDK4 but also other genes. Potential driver mutations were found in only six (11%) samples; however, gene amplification events (other than MDM2 and CDK4 amplification) were identified in 30 (54%) samples. Receptor tyrosine kinase (RTK) genes in particular were amplified in 18 (32%) samples. In addition, growth of a WDLPS cell line with IGF1R amplification was suppressed by simultaneous inhibition of CDK4 and IGF1R, using palbociclib and NVP-AEW541, respectively. Combination therapy with CDK4 and RTK inhibitors may be an effective therapeutic option for WDLPS/DDLPS patients with RTK gene amplification.

引用

页码：12941 / 12952

页数：12

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