DNA profiling of primary serous ovarian and Fallopian tube carcinomas with array comparative genomic hybridization and multiplex ligation-dependent probe amplification

M. E. Nowee, A. M. Snijders, D. A.P. Rockx, R. M. de Wit, V. M. Kosma, K. Hämäläinen, J. P. Schouten, R. H.M. Verheijen, P. J. van Diest, D. G. Albertson, J. C. Dorsman

Research output: Contribution to journalArticle

Abstract

Primary serous ovarian carcinoma (OVCA) and serous Fallopian tube carcinoma (FTC), both belonging to the BRCA-linked tumour spectrum, share many properties and are treated similarly. However, a detailed molecular comparison has been lacking. We hypothesized that comparative genomic studies of serous OVCAs; and FTCs should point to gene regions critically involved in their tumorigenesis. Array comparative genomic hybridization (array CGH) analysis indicated that serous OVCAs and serous FTCs displayed common but also more distinctive patterns of recurrent changes. Targeted gene identification using a dedicated multiplex ligation-dependent probe amplification (MLPA) probe set directly identified EIF2C2 on 8q as a potentially important driver gene. Other previously unappreciated gained/amplified genes included PSMB4 on 1q, MTSS1 on 8q, TEAD4 and TSPAN9 on 12p, and BCAS4 on 20q. SPINT2 and ACTN4 on 19q were predominantly found in FTCs. Gains/amplifications of CCNE1 and MYC, often in conjunction with changes in genes of the AKT pathway, EVI1 and PTK2, seemed to be involved at earlier stages, whereas changes of ERBB2 were associated with advanced stages. The only BRCA1-mutated FTC shared common denominators with the sporadic tumours. In conclusion, the data suggest that serous OVCAs and FTCs, although related, exhibit differences in genomic profiles. In addition to known pathways, new genes/pathways are likely to be involved, with changes in an miRNA-associated gene, EIF2C2, as one important new feature. Dedicated MLPA sets constitute potentially important tools for differential diagnosis and may provide footholds for tailored therapy.

Original languageEnglish (US)
Pages (from-to)46-55
Number of pages10
JournalJournal of Pathology
Volume213
Issue number1
DOIs
StatePublished - Sep 2007

Keywords

  • Array CGH
  • Fallopian tube carcinoma
  • MLPA
  • Ovarian carcinoma
  • Serous adenocarcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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  • Cite this

    Nowee, M. E., Snijders, A. M., Rockx, D. A. P., de Wit, R. M., Kosma, V. M., Hämäläinen, K., Schouten, J. P., Verheijen, R. H. M., van Diest, P. J., Albertson, D. G., & Dorsman, J. C. (2007). DNA profiling of primary serous ovarian and Fallopian tube carcinomas with array comparative genomic hybridization and multiplex ligation-dependent probe amplification. Journal of Pathology, 213(1), 46-55. https://doi.org/10.1002/path.2217