亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Charting co-mutation patterns associated with actionable drivers in intrahepatic cholangiocarcinoma

Wnt信号通路 微卫星不稳定性 拷贝数变化 医学 IDH1 肝内胆管癌 CDKN2A 肿瘤科 MAPK/ERK通路 表观遗传学 CDKN2B公司 癌症的体细胞进化 突变 癌症研究 内科学 生物信息学 基因 癌症 生物 遗传学 信号转导 微卫星 基因组 等位基因
作者
Gajanan Kendre,Karthikeyan Murugesan,Tilman Brummer,Oreste Segatto,Anna Saborowski,Arndt Vogel
出处
期刊:Journal of Hepatology [Elsevier]
卷期号:78 (3): 614-626 被引量:69
标识
DOI:10.1016/j.jhep.2022.11.030
摘要

In recent years, intrahepatic cholangiocarcinoma (iCCA) has evolved as a "role model" for precision oncology in gastrointestinal cancers. However, its rarity, paired with its genomic heterogeneity, challenges the development and evolution of targeted therapies. Interrogating large datasets drives better understanding of the characteristics of molecular subgroups of rare cancers and enables the identification of genomic patterns that remain unrecognized in smaller cohorts.We performed a retrospective analysis of 6,130 patients diagnosed with iCCA from the FoundationCORE database who received diagnostic panel sequencing on the FoundationOne platform. Short variants/fusion-rearrangements and copy number alterations in >300 tumor-associated genes were evaluated, and the tumor mutational burden (TMB) as well as the microsatellite instability (MSI) status were available for the majority of the cohort.We provide a highly representative cartography of the genomic landscape of iCCA and outline the co-mutational spectra of seven therapeutically relevant oncogenic driver genes: IDH1/2, FGFR2, ERBB2, BRAF, MDM2, BRCA1/2, MET and KRASG12C. We observed a negative selection of RTK/RAS/ERK pathway co-alterations, and an enrichment of epigenetic modifiers such as ARID1A and BAP1 in patients with IDH1/2 and FGFR2 alterations. RNF43 as well as KMT2D occurred with high frequency in MSIhigh and TMBhigh tumors.Detailed knowledge of the most prevalent genomic constellations is key to the development of effective treatment strategies for iCCA. Our study provides a valuable resource that could be used to assess the feasibility of clinical trials and subgroup analyses, spurs the development of translationally relevant preclinical models, and serves as a knowledge base to predict potential mechanisms of resistance to targeted therapies in genomically defined subgroups.Due to the high frequency of targetable alterations, molecular diagnostics is recommended in patients with biliary tract cancers, and especially in those with iCCA. The identification of an actionable lesion, however, does not guarantee therapeutic success, and the co-mutational spectrum may act as a critical modifier of drug response. Using a large dataset of comprehensive panel sequencing results from 6,130 patients with iCCA, we provide a detailed analysis of the co-mutational spectrum of the most frequent druggable genetic alterations, which is meant to serve as a reference to establish genetically relevant preclinical models, develop hypothesis-driven combination therapies and identify recurrent genetic profiles.
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
大幅提高文件上传限制,最高150M (2024-4-1)

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
SCI完成签到,获得积分10
10秒前
TIGun发布了新的文献求助10
12秒前
科研通AI2S应助机智秋天采纳,获得10
15秒前
TIGun完成签到,获得积分10
27秒前
51秒前
所所应助科研通管家采纳,获得30
58秒前
1分钟前
莱芙完成签到 ,获得积分10
1分钟前
vvan发布了新的文献求助10
1分钟前
1分钟前
1分钟前
1分钟前
lsx发布了新的文献求助10
2分钟前
lsx完成签到,获得积分10
2分钟前
2分钟前
南寅完成签到,获得积分10
2分钟前
谨慎颜演完成签到 ,获得积分10
2分钟前
2分钟前
研友_VZG7GZ应助科研通管家采纳,获得10
2分钟前
Jasper应助科研通管家采纳,获得10
2分钟前
Amber完成签到 ,获得积分10
3分钟前
wodetaiyangLLL完成签到 ,获得积分10
3分钟前
3分钟前
3分钟前
研友_VZG7GZ应助aaaaa采纳,获得10
4分钟前
4分钟前
aaaaa发布了新的文献求助20
4分钟前
vvan发布了新的文献求助10
4分钟前
樱桃猴子应助科研通管家采纳,获得10
4分钟前
樱桃猴子应助科研通管家采纳,获得10
4分钟前
5分钟前
micomico完成签到 ,获得积分10
5分钟前
魔幻的代珊应助LYL采纳,获得10
5分钟前
aaaaa完成签到,获得积分10
5分钟前
下次一定发布了新的文献求助10
5分钟前
6分钟前
丁宇卓完成签到 ,获得积分10
6分钟前
6分钟前
胡涛涛发布了新的文献求助10
6分钟前
传奇3应助harrywoo采纳,获得10
6分钟前
高分求助中
The ACS Guide to Scholarly Communication 2500
Sustainability in Tides Chemistry 2000
Pharmacogenomics: Applications to Patient Care, Third Edition 1000
Studien zur Ideengeschichte der Gesetzgebung 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 810
Genera Insectorum: Mantodea, Fam. Mantidæ, Subfam. Hymenopodinæ (Classic Reprint) 800
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3085426
求助须知:如何正确求助?哪些是违规求助? 2738274
关于积分的说明 7548805
捐赠科研通 2387902
什么是DOI,文献DOI怎么找? 1266200
科研通“疑难数据库(出版商)”最低求助积分说明 613332
版权声明 598569