Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor

Eric P. Kleinbaum, Alexander J.F. Lazar, Elena Tamborini, John C. McAuliffe, Pamela B. Sylvestre, Thomas D. Sunnenberg, Louise Strong, Lei L. Chen, Haesun Choi, Robert S. Benjamin, Wei Zhang, Jonathan C. Trent

Research output: Contribution to journalArticle

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Abstract

Germ-line mutations in the KIT receptor tyrosine kinase gene have been described in families with a propensity to develop gastrointestinal stromal tumor (GIST). There is limited information from large kindreds regarding median age at diagnosis, detailed histopathology, clinical effects of imatinib therapy and chromosomal abnormalities of the KIT gene. We identified a large kindred with GIST. Each family member was interviewed and appropriate medical records and radiographic imaging were obtained. Archival tumor tissue was obtained to confirm diagnosis, extract genomic DNA and perform fluorescent in situ hybridization cytogenetics of the KIT gene. Fifteen of 79 individuals with GIST were identified in this kindred. There were 8 males, the mean age at diagnosis was 53.9 (range 45-71) years. Histopathology revealed microscopic proliferation and nodularity in the myenteric plexus, spindled morphology, diffuse Kit but variable CD34 staining and low mitotic rates in the setting of metastatic disease. A deletion of codon 579 in exon 11 of the KIT gene was identified in tumor and normal tissue of this family. Mutation and cytogenetic analysis revealed homozygous loss of the wild-type KIT sequence in tumor from one individual. Four of 4 individuals treated with imatinib are alive and without progression while 9 of 11 individuals not treated with imatinib are deceased. This study describes a kindred with a propensity to develop GIST in an autosomal dominant pattern. Germ-line deletion of KIT codon 579 in GIST is associated with clinical benefit from imatinib, limited utility of mitoses to predict malignant potential, and a novel homozygous deletion of this codon in one individual.

Original languageEnglish (US)
Pages (from-to)711-718
Number of pages8
JournalInternational Journal of Cancer
Volume122
Issue number3
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

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Gastrointestinal Stromal Tumors
Codon
Genes
Therapeutics
Myenteric Plexus
Neoplasms
Germ-Line Mutation
Cytogenetic Analysis
Receptor Protein-Tyrosine Kinases
Fluorescence In Situ Hybridization
Mitosis
Germ Cells
Cytogenetics
Chromosome Aberrations
Medical Records
Exons
Staining and Labeling
Mutation
Imatinib Mesylate
DNA

Keywords

  • Genotype
  • Gleevec
  • Mutation
  • Sarcoma
  • Therapy

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Kleinbaum, E. P., Lazar, A. J. F., Tamborini, E., McAuliffe, J. C., Sylvestre, P. B., Sunnenberg, T. D., ... Trent, J. C. (2008). Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor. International Journal of Cancer, 122(3), 711-718. https://doi.org/10.1002/ijc.23137

Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor. / Kleinbaum, Eric P.; Lazar, Alexander J.F.; Tamborini, Elena; McAuliffe, John C.; Sylvestre, Pamela B.; Sunnenberg, Thomas D.; Strong, Louise; Chen, Lei L.; Choi, Haesun; Benjamin, Robert S.; Zhang, Wei; Trent, Jonathan C.

In: International Journal of Cancer, Vol. 122, No. 3, 01.02.2008, p. 711-718.

Research output: Contribution to journalArticle

Kleinbaum, EP, Lazar, AJF, Tamborini, E, McAuliffe, JC, Sylvestre, PB, Sunnenberg, TD, Strong, L, Chen, LL, Choi, H, Benjamin, RS, Zhang, W & Trent, JC 2008, 'Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor', International Journal of Cancer, vol. 122, no. 3, pp. 711-718. https://doi.org/10.1002/ijc.23137
Kleinbaum, Eric P. ; Lazar, Alexander J.F. ; Tamborini, Elena ; McAuliffe, John C. ; Sylvestre, Pamela B. ; Sunnenberg, Thomas D. ; Strong, Louise ; Chen, Lei L. ; Choi, Haesun ; Benjamin, Robert S. ; Zhang, Wei ; Trent, Jonathan C. / Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor. In: International Journal of Cancer. 2008 ; Vol. 122, No. 3. pp. 711-718.
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