OBJECTIVETo elucidate the mutation profiles of c-kit/PDGFRα and its associations with clinicopathological characteristics in large scale Chinese gastrointestinal stromal tumors(GISTs).

METHODSClinicopathological data and tumor samples of 1002 GIST patients treated in the Peking University Cancer Hospital from September 2002 to January 2014 were retrospectively collected. Mutation status of c-kit(exons 9, 11, 13, and 17) and PDGFRα(exons 12 and 18) genes were detected by direct sequencing. Association between mutation profiles and clinicopathological features of mutant patients were statistically analyzed.

RESULTSAmong all the 827 mutant patients, c-kit and PDGFRα mutations were found in 798 cases(96.5%, exons 11, 9, 13, and 17 mutations in 669, 99, 18, 12) and 29 cases (3.5%, exons 12 and 18 in 2 and 27), respectively. As for c-kit gene, deletion mutation was most frequent in exon 11(n=325), and then point mutation(n=172), mixed mutation(n=135), and duplication mutation(n=37). The duplication of codons 502-503 was the unique genotype for exon 9 of c-kit gene, and point mutation was the single mutation type for exons 13 and 17 of c-kit gene. Point mutation was the most common mutation for PDGFRα gene with few deletion or mixed mutations. Most deletion mutations of c-kit gene were located in 5' region of exon 11, duplication mutations were mainly located in 3' region of exon 11, and point mutations were focused on codons 556-560. Mutation type of exon 11 was associated with age, gender, primary location, tumor size, karyokinesis image and CD 34 expression(all P<0.05).

CONCLUSIONGISTs are featured by frequent gene mutations, many mutation types, and specificity for mutations in same exons or different exons.

The incidence of small and micro gastrointestinal stromal tumors is increasing significantly because of the enhanced health consciousness and advanced endoscopic technology. But there still is controversial in the biological behavior and clinical treatment of GIST. The treatment of the GIST with endoscopic technology has obvious advantages. This method can remove tumor and avoid significant trauma. In this paper, the biological behavior, clinical evaluation and endoscopic treatment of the GIST are discussed.
Endoscopy, Gastrointestinal ; Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; Humans

The emergence of small molecular tyrosine kinase inhibitors opened the era of targeted therapy of gastrointestinal stromal tumor(GIST). Survival and life of quality of patients from advanced stage are significantly improved by using targeted therapy. However, with prolonged treatment, drug resistance is becoming more and more common and directly affects the survival of patients. The current clinical management in failure of multi-line targeted therapies will be discussed in this article.
Antineoplastic Combined Chemotherapy Protocols ; Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; Humans ; Imatinib Mesylate ; Indoles ; Pyrroles

Tyrosine kinase inhibitor(TKI) combined with surgical treatment is the optimal strategy for gastrointestinal stromal tumors(GIST). However, there is no systemic report about the complicated GIST(recurrence or metastasis, peritoneal dissemination, combined resection of multiple organs), except the cases review and experimental studies. Tyrosine kinase inhibitor combined with surgery may increase the overall survival of complicated GIST. This article will describe the definition, clinical features, surgical and drug therapy, and prognosis, in order to provide reliable theoretical basis and experience for clinical doctors, prolong patient survival and improve the quality of survival.
Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; Humans ; Peritoneum ; Prognosis ; Protein Kinase Inhibitors

In order to promote clinical capability on duodenal gastrointestinal stromal tumor(GIST), literature review and experience summary were documented in this paper. Duodenal GIST is not rare in clinical practice. With the similar pathologic conditions, GIST in duodenum present a higher malignant risk than that in stomach. The cases who would receive imatinib mesylate as preoperative therapy require a precise preoperative diagnosis obtained by endoscopic ultrasound and fine needle aspiration cytology. Therapeutic strategy should be based on surgical R0 resection with clear margins, preserving pancreatic function and avoiding adjacent organs resection when possible. Limited resection is appropriate and results in similar oncological outcome compared with extensive procedure in suitable cases.
Duodenal Neoplasms ; Endosonography ; Gastrointestinal Stromal Tumors ; Humans ; Neoadjuvant Therapy ; Stomach

Imatinib is the key medication for adjuvant therapy in gastrointestinal stromal tumors(GIST) and the first line therapy for patients with metastatic or recurrent GIST. Preoperative treatment with imatinib may improve R0 resection rate and provide the chance of metastasectomy for cytoreduction as well as prolonging patient's survival. We investigate the significance of neoadjuvant therapy of imatinib and the timing of surgery by reviewing clinical trials and consensus in recent years.
Antineoplastic Agents ; Chemotherapy, Adjuvant ; Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; Humans ; Imatinib Mesylate ; Neoadjuvant Therapy

The biological behavior of gastrointestinal stromal tumor(GIST) is highly variable. To assess the risk of recurrence of the primary tumor accurately is a key challenge. The risk assessment system of GIST has experienced several revolutions. The present accepted risk stratification scheme is still to be consummated. The pathological morphological characteristics, mutational features, and other biomarkers are helpful to improve the risk assessment system. The risk assessment of GIST in the future will be more and more diversified.
Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; Humans ; Mutation ; Risk Assessment

Gastrointestinal stromal tumors(GISTs) are the most common gastrointestinal mesenchymal tumors of the gastrointestinal tract. Most of GISTs are characterized by mutation in the c-kit or PDGFR-α genes. In recent years, detection of gene mutation in GISTs has been widely used. In addition to the contribution to the diagnosis of difficult cases, such detection also has important value in predicting the efficacy of therapeutic drugs targeting, guiding clinical treatment and evaluating the prognosis of patients. In a word, gene mutation detection should be considered as the important standard for exact diagnosis and treatment of GISTs.
Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; Humans ; Mutation ; Prognosis ; Proto-Oncogene Proteins c-kit ; Receptor, Platelet-Derived Growth Factor alpha

Gastrointestinal stromal tumors(GIST) are the most common mesenchymal tumors in gastrointestinal tract. At present, surgical and molecular targeted therapies are the main treatments. Operation is properly the only way of radical resection. The general principles of surgery are complete resection of the tumor, negative margins, as well as no intraoperative tumor rupture. The choice of surgical skills for GIST is obviously affected by different locations. This paper reviews current literatures combined with our experiences, and elaborates relevant contents in detail.
Gastrointestinal Neoplasms ; Gastrointestinal Stromal Tumors ; Humans ; Molecular Targeted Therapy ; Neoplasms, Connective and Soft Tissue

Lymph node metastasis is one of the factors associated with the prognosis of gastric cancer patients. While precise evaluation of nodal status can promote the personalized surgery and improve prognosis. Although with many unsolved problems and limitations, radioimmune technique can be used to trace gastric cancer and metastatic lymph nodes. With the constant development of monoclonal antibody, genetic engineering antibody, nuclide molecular functional imaging, the radioimmune technique may allow tumor targeting, preoperative imaging, and intraoperative tracing. Therefore, more accurate tumor staging and optimal therapeutic regimen may be possible. This review mainly focuses on the utility of radioimmuno-tracing technique in metastatic lymph node for gastric cancer.
Antibodies, Monoclonal ; Disease Progression ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Stomach Neoplasms