Genome-Wide Analysis Identifies MEN1 and MAX Mutations and a Neuroendocrine-Like Molecular Heterogeneity in Quadruple WT GIST

PDGFRA公司 主旨 生物 门1 外显子组 间质瘤 癌症研究 遗传学 外显子组测序 种系突变
作者
Maria Abbondanza Pantaleo,Milena Urbini,Valentina Indio,Gloria Ravegnini,Margherita Nannini,Matilde De Luca,Giuseppe Tarantino,Sabrina Angelini,Alessandro Gronchi,Bruno Vincenzi,Giovanni Grignani,Chiara Colombo,Elena Fumagalli,Lidia Gatto,Maristella Saponara,Manuela Ianni,Paola Paterini,Donatella Santini,M. Giulia Pirini,Claudio Ceccarelli,Annalisa Altimari,Elisa Gruppioni,Salvatore Lorenzo Renne,Paola Collini,Silvia Stacchiotti,Giovanni Brandi,Paolo G. Casali,Antonio Daniele Pinna,Annalisa Astolfi,Guido Biasco
出处
期刊:Molecular Cancer Research [American Association for Cancer Research]
卷期号:15 (5): 553-562 被引量:40
标识
DOI:10.1158/1541-7786.mcr-16-0376
摘要

Abstract Quadruple wild-type (WT) gastrointestinal stromal tumor (GIST) is a genomic subgroup lacking KIT/PDGFRA/RAS pathway mutations, with an intact succinate dehydrogenase (SDH) complex. The aim of this work is to perform a wide comprehensive genomic study on quadruple WT GIST to improve the characterization of these patients. We selected 14 clinical cases of quadruple WT GIST, of which nine cases showed sufficient DNA quality for whole exome sequencing (WES). NF1 alterations were identified directly by WES. Gene expression from whole transcriptome sequencing (WTS) and miRNA profiling were performed using fresh-frozen, quadruple WT GIST tissue specimens and compared with SDH and KIT/PDGFRA-mutant GIST. WES identified an average of 18 somatic mutations per sample. The most relevant somatic oncogenic mutations identified were in TP53, MEN1, MAX, FGF1R, CHD4, and CTDNN2. No somatic alterations in NF1 were identified in the analyzed cohort. A total of 247 mRNA transcripts and 66 miRNAs were differentially expressed specifically in quadruple WT GIST. Overexpression of specific molecular markers (COL22A1 and CALCRL) and genes involved in neural and neuroendocrine lineage (ASCL1, Family B GPCRs) were detected and further supported by predicted miRNA target analysis. Quadruple WT GIST show a specific genetic signature that deviates significantly from that of KIT/PDGFRA-mutant and SDH-mutant GIST. Mutations in MEN1 and MAX genes, a neural-committed phenotype and upregulation of the master neuroendocrine regulator ASCL1, support a genetic similarity with neuroendocrine tumors, with whom they also share the great variability in oncogenic driver genes. Implications: This study provides novel insights into the biology of quadruple WT GIST that potentially resembles neuroendocrine tumors and should promote the development of specific therapeutic approaches. Mol Cancer Res; 15(5); 553–62. ©2017 AACR.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
peterlzb1234567完成签到,获得积分10
2秒前
natsu401完成签到 ,获得积分10
5秒前
mmddlj完成签到 ,获得积分10
5秒前
健康的雁凡完成签到,获得积分10
5秒前
稳重完成签到 ,获得积分10
7秒前
10秒前
haiqi完成签到,获得积分20
14秒前
白智妍发布了新的文献求助10
15秒前
王叮叮完成签到,获得积分10
16秒前
jeronimo完成签到,获得积分10
17秒前
17秒前
pcr163应助大橙子采纳,获得150
20秒前
李燕发布了新的文献求助10
22秒前
道友等等我完成签到,获得积分0
22秒前
狂野乌冬面完成签到 ,获得积分10
26秒前
xinglin完成签到 ,获得积分10
28秒前
清浅完成签到 ,获得积分10
28秒前
30秒前
31秒前
科奇完成签到,获得积分10
31秒前
可玩性完成签到 ,获得积分10
32秒前
要减肥岩完成签到,获得积分10
34秒前
Owen应助Snail采纳,获得10
36秒前
大橙子发布了新的文献求助10
36秒前
9239完成签到 ,获得积分10
37秒前
量子星尘发布了新的文献求助10
37秒前
songvv发布了新的文献求助10
37秒前
飒飒发布了新的文献求助10
38秒前
慧灰huihui完成签到,获得积分10
38秒前
Star完成签到,获得积分10
40秒前
40秒前
柔弱的不二完成签到,获得积分10
41秒前
无心的枫完成签到,获得积分10
43秒前
djdh完成签到 ,获得积分10
43秒前
肖果完成签到 ,获得积分10
46秒前
哭泣笑柳发布了新的文献求助10
47秒前
CipherSage应助长安采纳,获得10
48秒前
飒飒完成签到,获得积分10
49秒前
RONG完成签到 ,获得积分10
49秒前
落落完成签到,获得积分10
50秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038184
求助须知:如何正确求助?哪些是违规求助? 3575908
关于积分的说明 11373872
捐赠科研通 3305715
什么是DOI,文献DOI怎么找? 1819255
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022