ABSTRACT
Pathogenetic pathways of gastrointestinal stromal tumors (GIST) lacking mutations in KIT and PDGFRA (â¼15%) 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.
Subject(s)
Gastrointestinal Stromal Tumors/enzymology , Gastrointestinal Stromal Tumors/genetics , Mutation , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-kit/genetics , Receptor, Platelet-Derived Growth Factor alpha/genetics , Adult , Aged , Aged, 80 and over , Amino Acid Sequence , Class I Phosphatidylinositol 3-Kinases , DNA Mutational Analysis , Female , Gastrointestinal Stromal Tumors/pathology , Humans , Male , Middle Aged , Molecular Sequence Data , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins B-raf/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Signal TransductionABSTRACT
Rectal gastrointestinal stromal tumors are rare. To date, 12 gastrointestinal stromal tumors have been reported as pelvic vaginal masses. We describe a rectovaginal tumor in a 39-year-old woman. The tumor frequently recurred after multiple surgical excisions and interrupted imatinib treatment without metastasizing. Magnetic resonance tomography demonstrated a partial response under imatinib. The patient was alive with stable disease under imatinib 44 months from initial diagnosis. Molecular analysis showed a somatic 6-base pair deletion in exon 11 of c-KIT (W557_K558del) in both the primary tumor and the third recurrence; the recurrence had an additional exon 17 mutation (N822K). Comparative genomic hybridization analysis of the primary tumor showed loss of 14q and gain of 1q. Recurrence showed complete loss of nuclear p16 expression. Molecular studies and p16 status confirmed the typical characteristics of gastrointestinal stromal tumors with an aggressive phenotype underscoring the need for a special interdisciplinary treatment and for achieving complete local excision with free margins.
