|
|||||
|
|
KIT codon 558 insertions in gastrointestinal stromal tumors. Analysis of 17 rare KIT mutants |
|
| Authors: | Lasota Jerzy Kuban Wojciech Wardelmann Eva Debiec-Rychter Maria Merkelbach-Bruse Sabine Sciot Raf Rys Janusz Steigen Sonja E Iwanik Katarzyna Holden Joseph A Jerzak Vel Dobosz Anna Schildhaus Hans-Ulrich Miettinen Markku |
| Affiliation: | a Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA b Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3371, USA c Department of Pathology, University of Bonn Medical Center, 53127 Bonn, Germany d Department of Human Genetics, Catholic University of Leuven, B-3000 Leuven, Belgium e Department of Pathology, Catholic University of Leuven, B-3000 Leuven, Belgium f Department of Pathology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 31-115 Krakow, Poland g Department of Pathology, University of Tromsø, N-9037 Tromsø, Norway h Department of Pathomorphology, Karol Marcinkowski Medical University, 60-355 Poznań, Poland i Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84112, USA j Department of Molecula Biology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-784 Warszawa, Poland |
| Abstract: | Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of gastrointestinal tract often driven by oncogenic KIT exon 11 mutations. Although deletions and substitutions are most frequent KIT exon 11 mutations, duplications and insertions have been reported as well. In contrast to duplications, which cluster in 3′KIT exon 11, insertions affect 5′KIT, particularly codon 558. Clinicopathologic profile of gastrointestinal stromal tumors with insertions in codon 558 is not known. In this study, 17 gastrointestinal stromal tumors with codon 558 insertions are reported. Fifteen (88.2%) KIT codon 558 insertions consisted of 1694_1695insTCC leading to Lys558delinsAsnPro. However, 2 variant mutants Lys558delinsAsnGln and Lys558delinsAsnAsn were also identified. Based on analysis of inserted and flanking sequences, the insertions contain inverted DNA sequences of the opposite strand. Therefore, these insertions may develop due to a DNA strand switch during replication by DNA polymerases and by the effects of several different DNA repair processes. Patient median age was 61 years, and male-to-female ratio was 1:1.8. gastrointestinal stromal tumors were diagnosed in stomach (n = 4), small intestine (n = 7), and rectum (n = 3). Three tumors were disseminated and primary location could not be established. Fourteen tumors had spindle cell morphology, and epithelioid cell features were seen in 2 intestinal and 1 disseminated gastrointestinal stromal tumor. Based on size and mitotic activity, 2 (50%) of 4 gastric and 3 (48.9%) of 7 small intestinal gastrointestinal stromal tumors had more than 50% risk of metastases according to previous studies of gastrointestinal stromal tumor prognosis. All 3 rectal gastrointestinal stromal tumors were malignant. Metastases were verified in 8 (66.7%) of 12 patients with known clinical and follow-up data. In summary, KIT codon 558 insertions are rare mutations accounting for less than 1% of all KIT mutants. Gastrointestinal stromal tumors with these mutations appear to have predilection to female patients and intestinal location. Moreover, KIT codon 558 insertions might indicate an increased risk of malignant behavior for gastric gastrointestinal stromal tumors. |
| Keywords: | GIST KIT Exon 11 Insertion Mutation |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |