Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma - PubMed

Affiliations

• PMID: 22137795
• DOI: 10.1016/j.ccr.2011.11.005

Free article

Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma

Matija Snuderl et al. Cancer Cell. 2011.

Free article

Abstract

Tumor heterogeneity has been implicated in tumor growth and progression as well as resistance to therapy. We present an example of genetic heterogeneity in human malignant brain tumors in which multiple closely related driver genes are amplified and activated simultaneously in adjacent intermingled cells. We have observed up to three different receptor tyrosine kinases (EGFR, MET, PDGFRA) amplified in single tumors in different cells in a mutually exclusive fashion. Each subpopulation was actively dividing, and the genetic changes resulted in protein production, and coexisting subpopulations shared common early genetic mutations indicating their derivation from a single precursor cell. The stable coexistence of different clones within the same tumor will have important clinical implications for tumor resistance to targeted therapies.

Comment in

• Many tumors in one: a daunting therapeutic prospect.

  Ene CI, Fine HA. Ene CI, et al. Cancer Cell. 2011 Dec 13;20(6):695-7. doi: 10.1016/j.ccr.2011.11.018. Cancer Cell. 2011. PMID: 22172718

• Genetics: United colors of glioblastoma.

  Villanueva MT. Villanueva MT. Nat Rev Clin Oncol. 2012 Jan 10;9(2):68. doi: 10.1038/nrclinonc.2011.202. Nat Rev Clin Oncol. 2012. PMID: 22231761 No abstract available.

Similar articles

• Receptor tyrosine kinase genes amplified in glioblastoma exhibit a mutual exclusivity in variable proportions reflective of individual tumor heterogeneity.

  Little SE, Popov S, Jury A, Bax DA, Doey L, Al-Sarraj S, Jurgensmeier JM, Jones C. Little SE, et al. Cancer Res. 2012 Apr 1;72(7):1614-20. doi: 10.1158/0008-5472.CAN-11-4069. Epub 2012 Feb 6. Cancer Res. 2012. PMID: 22311673

• Amplification of genes encoding KIT, PDGFRalpha and VEGFR2 receptor tyrosine kinases is frequent in glioblastoma multiforme.

  Joensuu H, Puputti M, Sihto H, Tynninen O, Nupponen NN. Joensuu H, et al. J Pathol. 2005 Oct;207(2):224-31. doi: 10.1002/path.1823. J Pathol. 2005. PMID: 16021678

• Amplification of KIT, PDGFRA, VEGFR2, and EGFR in gliomas.

  Puputti M, Tynninen O, Sihto H, Blom T, Mäenpää H, Isola J, Paetau A, Joensuu H, Nupponen NN. Puputti M, et al. Mol Cancer Res. 2006 Dec;4(12):927-34. doi: 10.1158/1541-7786.MCR-06-0085. Mol Cancer Res. 2006. PMID: 17189383

• The MET oncogene in glioblastoma stem cells: implications as a diagnostic marker and a therapeutic target.

  Boccaccio C, Comoglio PM. Boccaccio C, et al. Cancer Res. 2013 Jun 1;73(11):3193-9. doi: 10.1158/0008-5472.CAN-12-4039. Epub 2013 May 21. Cancer Res. 2013. PMID: 23695554 Review.

• Molecular and cellular heterogeneity: the hallmark of glioblastoma.

  Aum DJ, Kim DH, Beaumont TL, Leuthardt EC, Dunn GP, Kim AH. Aum DJ, et al. Neurosurg Focus. 2014 Dec;37(6):E11. doi: 10.3171/2014.9.FOCUS14521. Neurosurg Focus. 2014. PMID: 25434380 Review.

Cited by

• Evolution and impact of subclonal mutations in chronic lymphocytic leukemia.

  Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K, Lawrence MS, Sougnez C, Stewart C, Sivachenko A, Wang L, Wan Y, Zhang W, Shukla SA, Vartanov A, Fernandes SM, Saksena G, Cibulskis K, Tesar B, Gabriel S, Hacohen N, Meyerson M, Lander ES, Neuberg D, Brown JR, Getz G, Wu CJ. Landau DA, et al. Cell. 2013 Feb 14;152(4):714-26. doi: 10.1016/j.cell.2013.01.019. Cell. 2013. PMID: 23415222 Free PMC article.

• Diffuse Gliomas with FGFR3-TACC3 Fusions: Oncogenic Mechanisms, Hallmarks, and Therapeutic Perspectives.

  Picca A, Sansone G, Santonocito OS, Mazzanti CM, Sanson M, Di Stefano AL. Picca A, et al. Cancers (Basel). 2023 Nov 23;15(23):5555. doi: 10.3390/cancers15235555. Cancers (Basel). 2023. PMID: 38067258 Free PMC article. Review.

• Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity.

  Meyer M, Reimand J, Lan X, Head R, Zhu X, Kushida M, Bayani J, Pressey JC, Lionel AC, Clarke ID, Cusimano M, Squire JA, Scherer SW, Bernstein M, Woodin MA, Bader GD, Dirks PB. Meyer M, et al. Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):851-6. doi: 10.1073/pnas.1320611111. Epub 2015 Jan 5. Proc Natl Acad Sci U S A. 2015. PMID: 25561528 Free PMC article.

• Emerging insights into the molecular and cellular basis of glioblastoma.

  Dunn GP, Rinne ML, Wykosky J, Genovese G, Quayle SN, Dunn IF, Agarwalla PK, Chheda MG, Campos B, Wang A, Brennan C, Ligon KL, Furnari F, Cavenee WK, Depinho RA, Chin L, Hahn WC. Dunn GP, et al. Genes Dev. 2012 Apr 15;26(8):756-84. doi: 10.1101/gad.187922.112. Genes Dev. 2012. PMID: 22508724 Free PMC article. Review.

• Feasibility, phase I, and phase II studies of tandutinib, an oral platelet-derived growth factor receptor-β tyrosine kinase inhibitor, in patients with recurrent glioblastoma.

  Batchelor TT, Gerstner ER, Ye X, Desideri S, Duda DG, Peereboom D, Lesser GJ, Chowdhary S, Wen PY, Grossman S, Supko JG. Batchelor TT, et al. Neuro Oncol. 2017 Apr 1;19(4):567-575. doi: 10.1093/neuonc/now185. Neuro Oncol. 2017. PMID: 27663390 Free PMC article. Clinical Trial.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • H1 Connect
  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal