Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Homologous recombination repair mechanisms in serous endometrial cancer

Jönsson, Jenny Maria LU ; Bååth, Maria LU ; Björnheden, Ida ; Sahin, Irem Durmaz LU ; Måsbäck, Anna LU and Hedenfalk, Ingrid LU orcid (2021) In Cancers 13(2).
Abstract

Serous endometrial cancer (SEC) resembles high-grade serous ovarian cancer (HGSOC) genetically and clinically, with recurrent copy number alterations, TP53 mutations and a poor prognosis. Thus, SEC patients may benefit from targeted treatments used in HGSOC, e.g., PARP inhibitors. However, the preclinical and clinical knowledge about SEC is scarce, and the exact role of defective DNA repair in this tumor subgroup is largely unknown. We aimed to outline the prevalence of homologous recombination repair deficiency (HRD), copy-number alterations, and somatic mutations in SEC. OncoScan SNP arrays were applied to 19 tumors in a consecutive SEC series to calculate HRD scores and explore global copy-number profiles and genomic aberrations.... (More)

Serous endometrial cancer (SEC) resembles high-grade serous ovarian cancer (HGSOC) genetically and clinically, with recurrent copy number alterations, TP53 mutations and a poor prognosis. Thus, SEC patients may benefit from targeted treatments used in HGSOC, e.g., PARP inhibitors. However, the preclinical and clinical knowledge about SEC is scarce, and the exact role of defective DNA repair in this tumor subgroup is largely unknown. We aimed to outline the prevalence of homologous recombination repair deficiency (HRD), copy-number alterations, and somatic mutations in SEC. OncoScan SNP arrays were applied to 19 tumors in a consecutive SEC series to calculate HRD scores and explore global copy-number profiles and genomic aberrations. Copy-number signatures were established and targeted sequencing of 27 HRD-associated genes was performed. All factors were examined in relation to HRD scores to investigate potential drivers of the HRD phenotype. Ten of the 19 SEC tumors (53%) had an HRD score > 42, considered to reflect an HRD phenotype. Higher HRD score was associated with loss of heterozygosity in key HRD genes, and copy-number signatures associated with non-BRCA1/2 dependent HRD in HGSOC. A high number of SECs display an HRD phenotype. It remains to be elucidated whether this also confers PARP inhibitor sensitivity.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Copy-number variation, DNA repair, Homologous recombination repair deficiency, PARP inhibition, Serous endometrial cancer
in
Cancers
volume
13
issue
2
article number
254
pages
15 pages
publisher
MDPI AG
external identifiers
  • pmid:33445465
  • scopus:85099402558
ISSN
2072-6694
DOI
10.3390/cancers13020254
language
English
LU publication?
yes
id
a88e4d98-b706-4749-987f-0197a0d4ed22
date added to LUP
2021-01-25 10:18:06
date last changed
2024-06-14 08:49:04
@article{a88e4d98-b706-4749-987f-0197a0d4ed22,
  abstract     = {{<p>Serous endometrial cancer (SEC) resembles high-grade serous ovarian cancer (HGSOC) genetically and clinically, with recurrent copy number alterations, TP53 mutations and a poor prognosis. Thus, SEC patients may benefit from targeted treatments used in HGSOC, e.g., PARP inhibitors. However, the preclinical and clinical knowledge about SEC is scarce, and the exact role of defective DNA repair in this tumor subgroup is largely unknown. We aimed to outline the prevalence of homologous recombination repair deficiency (HRD), copy-number alterations, and somatic mutations in SEC. OncoScan SNP arrays were applied to 19 tumors in a consecutive SEC series to calculate HRD scores and explore global copy-number profiles and genomic aberrations. Copy-number signatures were established and targeted sequencing of 27 HRD-associated genes was performed. All factors were examined in relation to HRD scores to investigate potential drivers of the HRD phenotype. Ten of the 19 SEC tumors (53%) had an HRD score &gt; 42, considered to reflect an HRD phenotype. Higher HRD score was associated with loss of heterozygosity in key HRD genes, and copy-number signatures associated with non-BRCA1/2 dependent HRD in HGSOC. A high number of SECs display an HRD phenotype. It remains to be elucidated whether this also confers PARP inhibitor sensitivity.</p>}},
  author       = {{Jönsson, Jenny Maria and Bååth, Maria and Björnheden, Ida and Sahin, Irem Durmaz and Måsbäck, Anna and Hedenfalk, Ingrid}},
  issn         = {{2072-6694}},
  keywords     = {{Copy-number variation; DNA repair; Homologous recombination repair deficiency; PARP inhibition; Serous endometrial cancer}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Homologous recombination repair mechanisms in serous endometrial cancer}},
  url          = {{http://dx.doi.org/10.3390/cancers13020254}},
  doi          = {{10.3390/cancers13020254}},
  volume       = {{13}},
  year         = {{2021}},
}