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Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin.

Publication ,  Journal Article
Vikeså, J; Møller, AKH; Kaczkowski, B; Borup, R; Winther, O; Henao, R; Krogh, A; Perell, K; Jensen, F; Daugaard, G; Nielsen, FC
Published in: BMC Cancer
March 19, 2015

BACKGROUND: Cancers of unknown primary (CUPs) constitute ~5% of all cancers. The tumors have an aggressive biological and clinical behavior. The aim of the present study has been to uncover whether CUPs exhibit distinct molecular features compared to metastases of known origin. METHODS: Employing genome wide transcriptome analysis, Linear Discriminant Analysis (LDA) and Quadratic Discriminant Analysis (QDA), we defined the putative origins of a large series of CUP and how closely related a particular CUP was to corresponding metastases of known origin. LDA predictions were subsequently used to define a universal CUP core set of differentially expressed genes, that by means of gene set enrichment analysis was exploited to depict molecular pathways characterizing CUP. RESULTS: The analyses show that CUPs are distinct from metastases of known origin. CUPs exhibit inconsistent expression of conventional cancer biomarkers and QDA derived outlier scores show that CUPs are more distantly related to their primary tumor class than corresponding metastases of known origin. Gene set enrichment analysis showed that CUPs display increased expression of genes involved in DNA damage repair and mRNA signatures of chromosome instability (CIN), indicating that CUPs are chromosome unstable compared to metastases of known origin. CONCLUSIONS: CIN may account for the uncommon clinical presentation, chemoresistance and poor outcome in patients with CUP and warrant selective diagnostic strategies and treatment.

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Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

March 19, 2015

Volume

15

Start / End Page

151

Location

England

Related Subject Headings

  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasms, Unknown Primary
  • Neoplasm Proteins
  • Neoplasm Metastasis
  • Male
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Female
 

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Vikeså, J., Møller, A. K. H., Kaczkowski, B., Borup, R., Winther, O., Henao, R., … Nielsen, F. C. (2015). Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin. BMC Cancer, 15, 151. https://doi.org/10.1186/s12885-015-1128-x
Vikeså, Jonas, Anne Kirstine H. Møller, Bogumil Kaczkowski, Rehannah Borup, Ole Winther, Ricardo Henao, Anders Krogh, et al. “Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin.BMC Cancer 15 (March 19, 2015): 151. https://doi.org/10.1186/s12885-015-1128-x.
Vikeså J, Møller AKH, Kaczkowski B, Borup R, Winther O, Henao R, et al. Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin. BMC Cancer. 2015 Mar 19;15:151.
Vikeså, Jonas, et al. “Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin.BMC Cancer, vol. 15, Mar. 2015, p. 151. Pubmed, doi:10.1186/s12885-015-1128-x.
Vikeså J, Møller AKH, Kaczkowski B, Borup R, Winther O, Henao R, Krogh A, Perell K, Jensen F, Daugaard G, Nielsen FC. Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin. BMC Cancer. 2015 Mar 19;15:151.
Journal cover image

Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

March 19, 2015

Volume

15

Start / End Page

151

Location

England

Related Subject Headings

  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasms, Unknown Primary
  • Neoplasm Proteins
  • Neoplasm Metastasis
  • Male
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Female