Whole-exome analysis of metaplastic breast carcinomas with extensive osseous differentiation Journal Article

   


Authors: Beca, F.; Sebastiao, A. P. M.; Pareja, F.; Dessources, K.; Lozada, J. R.; Geyer, F.; Selenica, P.; Zeizafoun, N.; Wen, H. Y.; Norton, L.; Brogi, E.; Weigelt, B.; Reis, J. S.
Article Title: Whole-exome analysis of metaplastic breast carcinomas with extensive osseous differentiation
Abstract: Aims Metaplastic breast carcinoma (MBC) is a rare type of triple-negative breast cancer that shows vast histological and genetic heterogeneity. Osseous differentiation can be found in different subtypes of MBC. Whether MBCs with osseous differentiation are underpinned by specific genetic alterations has yet to be defined. The aim of this study was to investigate the repertoire of somatic mutations and copy number alterations (CNAs) in three MBCs with extensive osseous differentiation. Methods and results Tumour and normal DNA samples from three MBCs with extensive osseous differentiation were subjected to whole-exome sequencing. Somatic mutations, CNAs and mutational signatures were determined by use of a validated bioinformatics pipeline. Our analyses revealed clonalTP53hotspot mutations associated with loss of heterozygosity of the wild-type allele coupled with mutations affecting genes related to the Wnt and/or the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathways in all cases analysed. All cases showed a dominant mutational signature 1, with two cases showing a secondary signature 3 in addition to other features of homologous recombination DNA repair defects. The oncostatin M receptor gene, which plays a role in mesenchymal differentiation and bone formation, was found to be mutated in two MBCs with extensive osseous differentiation and in none of 35 previously published 35 MBCs. Conclusion Our findings suggest that MBCs with osseous differentiation have somatic mutations similar to those of other forms of MBC.
Keywords: breast cancer; carcinoma; reveals; ubiquitin ligase; massively parallel sequencing; pi3k pathway; cancer; metaplastic breast
Journal Title: Histopathology
Volume: 77
Issue: 2
ISSN: 0309-0167
Publisher: Wiley Blackwell  
Date Published: 2020-08-01
Start Page: 321
End Page: 326
Language: English
ACCESSION: WOS:000555385600017
DOI: 10.1111/his.14088
PROVIDER: wos
PUBMED: 32043609
PMCID: PMC7518240
Notes: Article -- Source: Wos
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MSK Authors
  1. Larry Norton
    758 Norton
  2. Hannah Yong Wen
    301 Wen
  3. Edi Brogi
    515 Brogi
  4. Britta Weigelt
    632 Weigelt
  5. Jorge Sergio Reis-Filho
    639 Reis-Filho
  6. Fresia Gilda Pareja Zea
    216 Pareja Zea
  7. Felipe Correa Geyer
    107 Correa Geyer
  8. Pier Selenica
    189 Selenica
  9. John Roy Lozada
    20 Lozada
  10. Ana Paula Martins Sebastiao
    33 Martins Sebastiao
  11. Kimberly Dessources
    27 Dessources
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