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Proteogenomics decodes the evolution of human ipsilateral breast cancer

De Marchi, Tommaso LU ; Pyl, Paul Theodor LU ; Sjöström, Martin LU ; Reinsbach, Susanne Erika ; DiLorenzo, Sebastian ; Nystedt, Björn ; Tran, Lena LU ; Pekar, Gyula LU ; Wärnberg, Fredrik and Fredriksson, Irma , et al. (2023) In Communications Biology 6(1).
Abstract

Ipsilateral breast tumor recurrence (IBTR) is a clinically important event, where an isolated in-breast recurrence is a potentially curable event but associated with an increased risk of distant metastasis and breast cancer death. It remains unclear if IBTRs are associated with molecular changes that can be explored as a resource for precision medicine strategies. Here, we employed proteogenomics to analyze a cohort of 27 primary breast cancers and their matched IBTRs to define proteogenomic determinants of molecular tumor evolution. Our analyses revealed a relationship between hormonal receptors status and proliferation levels resulting in the gain of somatic mutations and copy number. This in turn re-programmed the transcriptome and... (More)

Ipsilateral breast tumor recurrence (IBTR) is a clinically important event, where an isolated in-breast recurrence is a potentially curable event but associated with an increased risk of distant metastasis and breast cancer death. It remains unclear if IBTRs are associated with molecular changes that can be explored as a resource for precision medicine strategies. Here, we employed proteogenomics to analyze a cohort of 27 primary breast cancers and their matched IBTRs to define proteogenomic determinants of molecular tumor evolution. Our analyses revealed a relationship between hormonal receptors status and proliferation levels resulting in the gain of somatic mutations and copy number. This in turn re-programmed the transcriptome and proteome towards a highly replicating and genomically unstable IBTRs, possibly enhanced by APOBEC3B. In order to investigate the origins of IBTRs, a second analysis that included primaries with no recurrence pinpointed proliferation and immune infiltration as predictive of IBTR. In conclusion, our study shows that breast tumors evolve into different IBTRs depending on hormonal status and proliferation and that immune cell infiltration and Ki-67 are significantly elevated in primary tumors that develop IBTR. These results can serve as a starting point to explore markers to predict IBTR formation and stratify patients for adjuvant therapy.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Communications Biology
volume
6
issue
1
article number
139
publisher
Nature Publishing Group
external identifiers
  • pmid:36732562
  • scopus:85147319675
ISSN
2399-3642
DOI
10.1038/s42003-023-04526-6
language
English
LU publication?
yes
id
068b6df1-7f80-45ef-8d05-78a6a3e62207
date added to LUP
2023-02-20 16:04:33
date last changed
2024-06-13 15:05:13
@article{068b6df1-7f80-45ef-8d05-78a6a3e62207,
  abstract     = {{<p>Ipsilateral breast tumor recurrence (IBTR) is a clinically important event, where an isolated in-breast recurrence is a potentially curable event but associated with an increased risk of distant metastasis and breast cancer death. It remains unclear if IBTRs are associated with molecular changes that can be explored as a resource for precision medicine strategies. Here, we employed proteogenomics to analyze a cohort of 27 primary breast cancers and their matched IBTRs to define proteogenomic determinants of molecular tumor evolution. Our analyses revealed a relationship between hormonal receptors status and proliferation levels resulting in the gain of somatic mutations and copy number. This in turn re-programmed the transcriptome and proteome towards a highly replicating and genomically unstable IBTRs, possibly enhanced by APOBEC3B. In order to investigate the origins of IBTRs, a second analysis that included primaries with no recurrence pinpointed proliferation and immune infiltration as predictive of IBTR. In conclusion, our study shows that breast tumors evolve into different IBTRs depending on hormonal status and proliferation and that immune cell infiltration and Ki-67 are significantly elevated in primary tumors that develop IBTR. These results can serve as a starting point to explore markers to predict IBTR formation and stratify patients for adjuvant therapy.</p>}},
  author       = {{De Marchi, Tommaso and Pyl, Paul Theodor and Sjöström, Martin and Reinsbach, Susanne Erika and DiLorenzo, Sebastian and Nystedt, Björn and Tran, Lena and Pekar, Gyula and Wärnberg, Fredrik and Fredriksson, Irma and Malmström, Per and Fernö, Mårten and Malmström, Lars and Malmstöm, Johan and Niméus, Emma}},
  issn         = {{2399-3642}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Communications Biology}},
  title        = {{Proteogenomics decodes the evolution of human ipsilateral breast cancer}},
  url          = {{http://dx.doi.org/10.1038/s42003-023-04526-6}},
  doi          = {{10.1038/s42003-023-04526-6}},
  volume       = {{6}},
  year         = {{2023}},
}