Chromosome 17 copy number changes in male breast cancer

Miangela M. Lacle, Cathy B. Moelans, Robert Kornegoor, Carmen van der Pol, Arjen J. Witkamp, Elsken van der Wall, Josef Rueschoff, Horst Buerger, Paul J. van Diest

Research output: Contribution to journalArticle

Abstract

Background: Overall, HER2-amplified female breast cancer (FBC) is associated with a high grade, an aggressive phenotype and a poor prognosis. In male breast cancer (MBC) amplification of HER2, located on chromosome 17, occurs at a lower frequency than in FBC, where it is part of complex rearrangements. So far, only few studies have addressed the occurrence of chromosome 17 alterations in small MBC cohorts. Methods: Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used to detect and characterize copy number changes on chromosome 17 in a cohort of 139 MBC. The results obtained were compared to those in FBC, and were correlated with clinicopathological features and patient outcome data. Results: We observed a lower frequency of chromosome 17 copy number changes with less complex rearrangement patterns in MBC compared to FBC. Chromosome 17 changes in MBC included gains of 17q and losses of 17p. Whole chromosome 17 polyploidies were not encountered. Two recurrent chromosome 17 amplicons were detected: on 17q12 (encompassing the NEUROD2, HER2, GRB7 and IKZF3 gens) and on 17q23.1 (encompassing the MIR21 and RPS6KB1 genes). Whole arm copy number gains of 17q were associated with decreased 5 year survival rates (p = 0.010). Amplification of HER2 was associated with a high tumor grade, but did not predict patient survival. Although copy number gains of HER2 and NEUROD2 were associated with a high tumor grade, a high mitotic count and a decreased 5 year survival rate (p = 0.015), only tumor size and NEUROD2 copy number gains emerged as independent prognostic factors. Conclusions: In MBC chromosome 17 shows less complex rearrangements and fewer copy number changes compared to FBC. Frequent gains of 17q, encompassing two distinct amplicons, and losses of 17p were observed, but no whole chromosome 17 polyploidies. Only NEUROD2 gains seem to have an independent prognostic impact. These results suggest different roles of chromosome 17 aberrations in male versus female breast carcinogenesis.

Original languageEnglish (US)
Pages (from-to)237-245
Number of pages9
JournalCellular Oncology
Volume38
Issue number3
DOIs
StatePublished - Apr 24 2015
Externally publishedYes

Fingerprint

Male Breast Neoplasms
Chromosomes, Human, Pair 17
Breast Neoplasms
Polyploidy
Survival Rate
Neoplasms
Multiplex Polymerase Chain Reaction
Fluorescence In Situ Hybridization
Chromosome Aberrations
Carcinogenesis
Breast
Arm

Keywords

  • Copy number changes
  • Male breast cancer
  • Multiplex ligation-dependent probe amplification
  • Oncogenes

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Lacle, M. M., Moelans, C. B., Kornegoor, R., van der Pol, C., Witkamp, A. J., van der Wall, E., ... van Diest, P. J. (2015). Chromosome 17 copy number changes in male breast cancer. Cellular Oncology, 38(3), 237-245. https://doi.org/10.1007/s13402-015-0227-7

Chromosome 17 copy number changes in male breast cancer. / Lacle, Miangela M.; Moelans, Cathy B.; Kornegoor, Robert; van der Pol, Carmen; Witkamp, Arjen J.; van der Wall, Elsken; Rueschoff, Josef; Buerger, Horst; van Diest, Paul J.

In: Cellular Oncology, Vol. 38, No. 3, 24.04.2015, p. 237-245.

Research output: Contribution to journalArticle

Lacle, MM, Moelans, CB, Kornegoor, R, van der Pol, C, Witkamp, AJ, van der Wall, E, Rueschoff, J, Buerger, H & van Diest, PJ 2015, 'Chromosome 17 copy number changes in male breast cancer', Cellular Oncology, vol. 38, no. 3, pp. 237-245. https://doi.org/10.1007/s13402-015-0227-7
Lacle MM, Moelans CB, Kornegoor R, van der Pol C, Witkamp AJ, van der Wall E et al. Chromosome 17 copy number changes in male breast cancer. Cellular Oncology. 2015 Apr 24;38(3):237-245. https://doi.org/10.1007/s13402-015-0227-7
Lacle, Miangela M. ; Moelans, Cathy B. ; Kornegoor, Robert ; van der Pol, Carmen ; Witkamp, Arjen J. ; van der Wall, Elsken ; Rueschoff, Josef ; Buerger, Horst ; van Diest, Paul J. / Chromosome 17 copy number changes in male breast cancer. In: Cellular Oncology. 2015 ; Vol. 38, No. 3. pp. 237-245.
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abstract = "Background: Overall, HER2-amplified female breast cancer (FBC) is associated with a high grade, an aggressive phenotype and a poor prognosis. In male breast cancer (MBC) amplification of HER2, located on chromosome 17, occurs at a lower frequency than in FBC, where it is part of complex rearrangements. So far, only few studies have addressed the occurrence of chromosome 17 alterations in small MBC cohorts. Methods: Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used to detect and characterize copy number changes on chromosome 17 in a cohort of 139 MBC. The results obtained were compared to those in FBC, and were correlated with clinicopathological features and patient outcome data. Results: We observed a lower frequency of chromosome 17 copy number changes with less complex rearrangement patterns in MBC compared to FBC. Chromosome 17 changes in MBC included gains of 17q and losses of 17p. Whole chromosome 17 polyploidies were not encountered. Two recurrent chromosome 17 amplicons were detected: on 17q12 (encompassing the NEUROD2, HER2, GRB7 and IKZF3 gens) and on 17q23.1 (encompassing the MIR21 and RPS6KB1 genes). Whole arm copy number gains of 17q were associated with decreased 5 year survival rates (p = 0.010). Amplification of HER2 was associated with a high tumor grade, but did not predict patient survival. Although copy number gains of HER2 and NEUROD2 were associated with a high tumor grade, a high mitotic count and a decreased 5 year survival rate (p = 0.015), only tumor size and NEUROD2 copy number gains emerged as independent prognostic factors. Conclusions: In MBC chromosome 17 shows less complex rearrangements and fewer copy number changes compared to FBC. Frequent gains of 17q, encompassing two distinct amplicons, and losses of 17p were observed, but no whole chromosome 17 polyploidies. Only NEUROD2 gains seem to have an independent prognostic impact. These results suggest different roles of chromosome 17 aberrations in male versus female breast carcinogenesis.",
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AU - Lacle, Miangela M.

AU - Moelans, Cathy B.

AU - Kornegoor, Robert

AU - van der Pol, Carmen

AU - Witkamp, Arjen J.

AU - van der Wall, Elsken

AU - Rueschoff, Josef

AU - Buerger, Horst

AU - van Diest, Paul J.

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N2 - Background: Overall, HER2-amplified female breast cancer (FBC) is associated with a high grade, an aggressive phenotype and a poor prognosis. In male breast cancer (MBC) amplification of HER2, located on chromosome 17, occurs at a lower frequency than in FBC, where it is part of complex rearrangements. So far, only few studies have addressed the occurrence of chromosome 17 alterations in small MBC cohorts. Methods: Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used to detect and characterize copy number changes on chromosome 17 in a cohort of 139 MBC. The results obtained were compared to those in FBC, and were correlated with clinicopathological features and patient outcome data. Results: We observed a lower frequency of chromosome 17 copy number changes with less complex rearrangement patterns in MBC compared to FBC. Chromosome 17 changes in MBC included gains of 17q and losses of 17p. Whole chromosome 17 polyploidies were not encountered. Two recurrent chromosome 17 amplicons were detected: on 17q12 (encompassing the NEUROD2, HER2, GRB7 and IKZF3 gens) and on 17q23.1 (encompassing the MIR21 and RPS6KB1 genes). Whole arm copy number gains of 17q were associated with decreased 5 year survival rates (p = 0.010). Amplification of HER2 was associated with a high tumor grade, but did not predict patient survival. Although copy number gains of HER2 and NEUROD2 were associated with a high tumor grade, a high mitotic count and a decreased 5 year survival rate (p = 0.015), only tumor size and NEUROD2 copy number gains emerged as independent prognostic factors. Conclusions: In MBC chromosome 17 shows less complex rearrangements and fewer copy number changes compared to FBC. Frequent gains of 17q, encompassing two distinct amplicons, and losses of 17p were observed, but no whole chromosome 17 polyploidies. Only NEUROD2 gains seem to have an independent prognostic impact. These results suggest different roles of chromosome 17 aberrations in male versus female breast carcinogenesis.

AB - Background: Overall, HER2-amplified female breast cancer (FBC) is associated with a high grade, an aggressive phenotype and a poor prognosis. In male breast cancer (MBC) amplification of HER2, located on chromosome 17, occurs at a lower frequency than in FBC, where it is part of complex rearrangements. So far, only few studies have addressed the occurrence of chromosome 17 alterations in small MBC cohorts. Methods: Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used to detect and characterize copy number changes on chromosome 17 in a cohort of 139 MBC. The results obtained were compared to those in FBC, and were correlated with clinicopathological features and patient outcome data. Results: We observed a lower frequency of chromosome 17 copy number changes with less complex rearrangement patterns in MBC compared to FBC. Chromosome 17 changes in MBC included gains of 17q and losses of 17p. Whole chromosome 17 polyploidies were not encountered. Two recurrent chromosome 17 amplicons were detected: on 17q12 (encompassing the NEUROD2, HER2, GRB7 and IKZF3 gens) and on 17q23.1 (encompassing the MIR21 and RPS6KB1 genes). Whole arm copy number gains of 17q were associated with decreased 5 year survival rates (p = 0.010). Amplification of HER2 was associated with a high tumor grade, but did not predict patient survival. Although copy number gains of HER2 and NEUROD2 were associated with a high tumor grade, a high mitotic count and a decreased 5 year survival rate (p = 0.015), only tumor size and NEUROD2 copy number gains emerged as independent prognostic factors. Conclusions: In MBC chromosome 17 shows less complex rearrangements and fewer copy number changes compared to FBC. Frequent gains of 17q, encompassing two distinct amplicons, and losses of 17p were observed, but no whole chromosome 17 polyploidies. Only NEUROD2 gains seem to have an independent prognostic impact. These results suggest different roles of chromosome 17 aberrations in male versus female breast carcinogenesis.

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