Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas Journal Article


Authors: Girard, N.; Shen, R.; Guo, T.; Zakowski, M. F.; Heguy, A.; Riely, G. J.; Huang, J.; Lau, C.; Lash, A. E.; Ladanyi, M.; Viale, A.; Antonescu, C. R.; Travis, W. D.; Rusch, V. W.; Kris, M. G.; Pao, W.
Article Title: Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas
Abstract: Purpose: Thymomas and thymic carcinomas are rare intrathoracic malignancies that can be invasive and refractory to conventional treatment. Because these tumors both originate from the thymus, they are often grouped together clinically. However, whether the underlying biology of these tumors warrants such clustering is unclear, and the optimum treatment of either entity is unknown. Experimental Design: All thymic tumors were profiled for mutations in genes encoding components of the EGFR and KIT signaling pathways, assessed for EGFR and KIT expression by immunohistochemistry, and analyzed by array-based comparative genomic hybridization. Previously untreated tumors were subjected to global gene expression arrays. Results: We analyzed 45 thymic tumors [thymoma, n = 38 (type A, n = 8; type B2, n = 22; type B3, n = 8); thymic carcinoma, n = 7]. One thymoma and one thymic carcinoma harbored KRAS mutations (G12A and G12V, respectively), and one thymoma had a G13V HRAS mutation. Three tumors displayed strong KIT staining. Two thymic carcinomas harbored somatic KIT mutations (V560del and H697Y). In cell viability assays, the V560del mutant was associated with similar sensitivities to imatinib and sunitinib, whereas the H697Y mutant displayed greater sensitivity to sunitinib. Genomic profiling revealed distinct differences between type A to B2 thymomas versus type B3 and thymic carcinomas. Moreover, array-based comparative genomic hybridization could readily distinguish squamous cell carcinomas of the thymus versus the lung, which can often present a diagnostic challenge. Conclusions: Comprehensive genomic analysis suggests that thymic carcinomas are molecularly distinct from thymomas. These data have clinical, pathologic, and therapeutic implications for the treatment of thymic malignancies. © 2009 American Association for Cancer Research.
Keywords: immunohistochemistry; signal transduction; adult; clinical article; human tissue; aged; middle aged; unclassified drug; gene mutation; mutation; sunitinib; genetic analysis; cell viability; imatinib; stem cell factor; proto-oncogene proteins c-kit; cluster analysis; gene expression; epidermal growth factor receptor; receptor, epidermal growth factor; oncogene h ras; oligonucleotide array sequence analysis; carcinoma; genomics; lung carcinoma; nucleic acid hybridization; thymoma; k ras protein; comparative genomic hybridization; sunitib malate; thorax tumor; thymic carcinoma; thymus neoplasms
Journal Title: Clinical Cancer Research
Volume: 15
Issue: 22
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2009-11-15
Start Page: 6790
End Page: 6799
Language: English
DOI: 10.1158/1078-0432.ccr-09-0644
PUBMED: 19861435
PROVIDER: scopus
PMCID: PMC2783876
DOI/URL:
Notes: --- - "Cited By (since 1996): 9" - "Export Date: 30 November 2010" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Adriana Heguy
    85 Heguy
  2. Valerie W Rusch
    652 Rusch
  3. Ronglai Shen
    127 Shen
  4. Cristina R Antonescu
    606 Antonescu
  5. William Pao
    141 Pao
  6. Nicolas Gerald Girard
    17 Girard
  7. James Huang
    119 Huang
  8. Marc Ladanyi
    863 Ladanyi
  9. Caroline Lau
    2 Lau
  10. William D Travis
    548 Travis
  11. Gregory J Riely
    344 Riely
  12. Maureen F Zakowski
    275 Zakowski
  13. Agnes Viale
    205 Viale
  14. Alex E Lash
    24 Lash
  15. Tianhua Guo
    22 Guo
  16. Mark Kris
    597 Kris