胃肠道间质瘤（GIST）中 KIT/PDGFRA/BRAF 突变和磷脂酰肌醇-3-激酶通路基因改变的谱。

Spectrum of KIT/PDGFRA/BRAF mutations and Phosphatidylinositol-3-Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST).

机构信息

Institute of Pathology, University Erlangen, Germany.

出版信息

Cancer Lett. 2011 Dec 15;312(1):43-54. doi: 10.1016/j.canlet.2011.07.029. Epub 2011 Aug 6.

DOI:10.1016/j.canlet.2011.07.029

PMID:21906875

Abstract

Pathogenetic pathways of gastrointestinal stromal tumors (GIST) lacking mutations in KIT and PDGFRA (∼15%) are still poorly studied. Nearly nothing is known about PI3K alterations in GISTs and only a few GISTs with BRAF mutations have been reported. BRAF mutations (V600E) were found in 3/87 tumors (3.5%) concomitantly were wild type for KIT and PDGFRA. No mutations were detected in KRAS, NRAS, and FGFR3. For the first-time we demonstrated a PIK3CA mutation (H1047L) simultaneously occurring with a 15-bp deletion in KIT exon 11 in one tumor. We suggest that BRAF mutations are of pathogenetic significance in wild type GISTs. The PI3K pathway should be assessed in future studies.

摘要

胃肠道间质瘤（GIST）中缺乏 KIT 和 PDGFRA 突变（约 15%）的发病机制途径仍研究甚少。几乎不了解 GIST 中的 PI3K 改变，并且仅报道了少数具有 BRAF 突变的 GIST。在 3/87 例肿瘤（3.5%）中同时发现 BRAF 突变（V600E），这些肿瘤的 KIT 和 PDGFRA 均为野生型。未在 KRAS、NRAS 和 FGFR3 中检测到突变。我们首次证明了在一个肿瘤中同时发生 PIK3CA 突变（H1047L）和 KIT 外显子 11 中的 15 个碱基缺失。我们认为，BRAF 突变在野生型 GIST 中具有发病意义。在未来的研究中应该评估 PI3K 途径。