Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature

Prakash, S., Sarran, L., Socci, N., DeMatteo, R. P., Eisenstat, J., Greco, A. M., Maki, R. G., Wexler, L. H., LaQuaglia, M. P., Besmer, P., Antonescu, C. R. (April 2005) Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature. J Pediatr Hematol Oncol, 27 (4). pp. 179-87. ISSN 1077-4114 (Print)1077-4114 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/15838387
DOI: 10.1097/01.mph.0000157790.81329.47

Abstract

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the intestinal tract that typically occur in adults over the age of 40 years. GISTs in younger patients are rare and not well characterized. The objective was to define the characteristics of GISTs in children and young adults (<30 years old). Clinicopathologic and molecular features, including KIT/PDGFRA genotype, in GISTs from 5 children and 10 young adults were analyzed. Gene expression analysis was performed on 5 gastric tumor samples from 2 children, 2 gastric tumors from young adults, and 10 gastric GISTs from older adults using an U133A Affymetrix platform (22,000 genes). All five pediatric GISTs occurred in girls, involved the stomach as multiple nodules, showed predominantly an epithelioid morphology, often involved lymph nodes, and lacked KIT or PDGFRA mutations. Although all five patients developed recurrence (four in the liver, three in the peritoneum, and two in both sites), four are still alive with disease. Of the 10 GISTs in young adults, half occurred in the small bowel and had spindle cell morphology, and one case had lymph node metastasis. KIT mutations were identified in seven cases, four in exon 11 and three in exon 9. Seven patients developed recurrence, and at last follow-up two patients had died of disease. Gene expression analysis showed high expression of PHKA1, FZD2, NLGN4, IGF1R, and ANK3 in the pediatric and young adult versus older adult cases. GISTs that occur in children are a separate clinicopathologic and molecular subset with predilection for girls, multifocal gastric tumors, and wild-type KIT/PDGFRA genotype. In contrast, GISTs in young adults are a more heterogeneous group, including cases that resemble either the pediatric or the older adult-type tumors. The distinct gene expression profile suggests avenues for investigation of pathogenesis and potential therapeutic strategies.

Item Type: Paper
Uncontrolled Keywords: Adolescent Adult Amino Acid Sequence Antineoplastic Agents/therapeutic use Benzamides Biomarkers, Tumor/*genetics Child DNA Mutational Analysis Female Gastrointestinal Stromal Tumors/drug therapy/*genetics/*pathology Gene Expression Profiling *Gene Expression Regulation, Neoplastic Humans Imatinib Mesylate Male Molecular Sequence Data Neoplasm Recurrence, Local/drug therapy Oligonucleotide Array Sequence Analysis Piperazines/therapeutic use Protein-Tyrosine Kinases/antagonists & inhibitors Proto-Oncogene Proteins c-kit/*genetics Pyrimidines/therapeutic use Receptor, Platelet-Derived Growth Factor alpha/*genetics Sequence Homology, Amino Acid
Subjects: organism description > animal > developmental stage > child
diseases & disorders > cancer > cancer types > gastrointestinal stromal tumors
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: April 2005
Date Deposited: 26 Oct 2016 19:42
Last Modified: 26 Oct 2016 19:42
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33663

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