PATH-38. APC MUTATION AS A DRIVER ONCOGENE IN NON-CTNNB1 MUTANT ADAMANTINOMATOUS CRANIOPHARYNGIOMAS

颅咽管瘤 Wnt信号通路 体细胞 生物 癌症研究 外显子组测序 种系突变 突变 病理 医学 信号转导 内分泌学 遗传学 基因
作者
Christopher S. Hong,Zeynep Erson-Omay,Sacit Bulent Omay
出处
期刊:Neuro-oncology [Oxford University Press]
卷期号:23 (Supplement_6): vi123-vi123
标识
DOI:10.1093/neuonc/noab196.490
摘要

Abstract Craniopharyngiomas arise from the embryonic remnants of Rathke’s pouch in the craniopharyngeal duct. Their invasive capacity and geographic proximity to the optic apparatus, pituitary gland and stalk, third ventricle, and the hypothalamus can cause progressive visual, hormonal, and neurological deficits and transform these lesions into behaviorally malignant tumors. The classic subtypes of craniopharyngiomas, adamantinomatous and papillary, have conventionally been approached similarly in regards to therapeutic strategies. However, recent exome sequencing studies have revealed mutually exclusive pathways for their genetic origins. Recurrent mutations in BRAF (V600E), a regulator of MAP kinase/ERK signaling pathway have been observed in 95% of papillary craniopharyngiomas and may be amenable to targeted therapies with BRAF inhibitors. However, CTNNB1 mutations are observed in only 75%–96% of adamantinomatous craniopharyngiomas, revealing a gap in the classic genetic-histological correlation. We describe a 74-year-old male who underwent resection of a craniopharyngioma with suprasellar and third ventricular involvement. The pathology demonstrated adamantinomatous craniopharyngioma with aberrant nuclear beta-catenin activity on immunohistochemistry. Whole-exome sequencing, performed in accordance with an institutional review board-approved protocol on the tumor and blood, revealed wildtype CTNNB1 but notably two somatic stop-codon mutations in APC (rs786201856:c.C793T:p.R265X and rs587779780:c.1159T:p.R387X), considered pathogenic variants in other reported cancer types. Loss of APC leads to constitutive activation of the Wnt signaling pathway, similar to the observed downstream effects of activating CTNNB1 mutations in adamantinomatous craniopharyngioma. Our case suggests that craniopharyngiomas may arise from somatic loss of APC, which previously was only described in a handful of individuals with familial adenomatous polyposis, harboring germline APC mutations. This report adds new insight into the pathogenesis of adamantinomatous craniopharyngiomas, particularly those that are otherwise wildtype for CTNNB1. Based on accumulating evidence, we propose that along with BRAF and CTNNB1, APC should also be routinely checked in cranipharyngiomas, especially if the former two have been negative.
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
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
寒冷河马完成签到,获得积分10
刚刚
2秒前
SCI狂徒邓超完成签到,获得积分10
4秒前
君知完成签到,获得积分10
7秒前
11秒前
YYA完成签到 ,获得积分10
12秒前
赵赵完成签到,获得积分10
14秒前
18秒前
Utopia完成签到,获得积分10
18秒前
看天边的云完成签到,获得积分10
20秒前
20秒前
21秒前
科研通AI2S应助科研达人采纳,获得30
24秒前
紫金大萝卜完成签到,获得积分0
24秒前
我是你爹发布了新的文献求助10
24秒前
菠萝吹雪应助看天边的云采纳,获得10
25秒前
干净幻梦完成签到,获得积分10
27秒前
28秒前
28秒前
张zhang应助wpie99采纳,获得10
29秒前
30秒前
南风完成签到,获得积分10
35秒前
思源应助孤独的面包采纳,获得10
36秒前
36秒前
everglow给bbecky的求助进行了留言
38秒前
静书发布了新的文献求助30
41秒前
左丘完成签到,获得积分10
42秒前
43秒前
44秒前
端庄的小蝴蝶完成签到,获得积分10
47秒前
李沐梓发布了新的文献求助10
49秒前
不安平凡完成签到,获得积分10
50秒前
大气的乌冬面完成签到,获得积分10
50秒前
科研菜鸟完成签到,获得积分10
50秒前
grey完成签到,获得积分10
52秒前
123干嘛呢应助静书采纳,获得10
54秒前
飘逸小笼包完成签到,获得积分10
54秒前
幽默的忆霜完成签到 ,获得积分10
54秒前
57秒前
57秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2500
Востребованный временем 2500
Agaricales of New Zealand 1: Pluteaceae - Entolomataceae 1040
지식생태학: 생태학, 죽은 지식을 깨우다 600
海南省蛇咬伤流行病学特征与预后影响因素分析 500
Neuromuscular and Electrodiagnostic Medicine Board Review 500
ランス多機能化技術による溶鋼脱ガス処理の高効率化の研究 500
热门求助领域 (近24小时)
化学 医学 材料科学 生物 工程类 有机化学 生物化学 纳米技术 内科学 物理 化学工程 计算机科学 复合材料 基因 遗传学 物理化学 催化作用 细胞生物学 免疫学 电极
热门帖子
关注 科研通微信公众号,转发送积分 3461213
求助须知:如何正确求助?哪些是违规求助? 3054925
关于积分的说明 9045546
捐赠科研通 2744821
什么是DOI,文献DOI怎么找? 1505702
科研通“疑难数据库(出版商)”最低求助积分说明 695786
邀请新用户注册赠送积分活动 695205