Genome instability in blood cells of a BRCA1+ breast cancer family

Fengxia Xiao, Yeong C. Kim, Carrie Snyder, Hongxiu Wen, Pei X. Chen, Jiangtao Luo, Dina Becirovic, Bradley Downs, Kenneth H. Cowan, Henry T. Lynch, San M. Wang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: BRCA1 plays an essential role in maintaining genome stability. Inherited BRCA1 germline mutation (BRCA1+) is a determined genetic predisposition leading to high risk of breast cancer. While BRCA1+ induces breast cancer by causing genome instability, most of the knowledge is known about somatic genome instability in breast cancer cells but not germline genome instability.Methods: Using the exome-sequencing method, we analyzed the genomes of blood cells in a typical BRCA1+ breast cancer family with an exon 13-duplicated founder mutation, including six breast cancer-affected and two breast cancer unaffected members.Results: We identified 23 deleterious mutations in the breast cancer-affected family members, which are absent in the unaffected members. Multiple mutations damaged functionally important and breast cancer-related genes, including transcriptional factor BPTF and FOXP1, ubiquitin ligase CUL4B, phosphorylase kinase PHKG2, and nuclear receptor activator SRA1. Analysis of the mutations between the mothers and daughters shows that most mutations were germline mutation inherited from the ancestor(s) while only a few were somatic mutation generated de novo.Conclusion: Our study indicates that BRCA1+ can cause genome instability with both germline and somatic mutations in non-breast cells.

Original languageEnglish
Article number342
JournalBMC Cancer
Volume14
Issue number1
DOIs
StatePublished - May 19 2014

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Genomic Instability
Blood Cells
Breast Neoplasms
Mutation
Germ-Line Mutation
Phosphorylase Kinase
Exome
Neoplasm Genes
Genetic Predisposition to Disease
Ligases
Cytoplasmic and Nuclear Receptors
Ubiquitin
Nuclear Family
Exons
Mothers
Genome

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research
  • Genetics
  • Medicine(all)

Cite this

Xiao, F., Kim, Y. C., Snyder, C., Wen, H., Chen, P. X., Luo, J., ... Wang, S. M. (2014). Genome instability in blood cells of a BRCA1+ breast cancer family. BMC Cancer, 14(1), [342]. https://doi.org/10.1186/1471-2407-14-342

Genome instability in blood cells of a BRCA1+ breast cancer family. / Xiao, Fengxia; Kim, Yeong C.; Snyder, Carrie; Wen, Hongxiu; Chen, Pei X.; Luo, Jiangtao; Becirovic, Dina; Downs, Bradley; Cowan, Kenneth H.; Lynch, Henry T.; Wang, San M.

In: BMC Cancer, Vol. 14, No. 1, 342, 19.05.2014.

Research output: Contribution to journalArticle

Xiao, F, Kim, YC, Snyder, C, Wen, H, Chen, PX, Luo, J, Becirovic, D, Downs, B, Cowan, KH, Lynch, HT & Wang, SM 2014, 'Genome instability in blood cells of a BRCA1+ breast cancer family', BMC Cancer, vol. 14, no. 1, 342. https://doi.org/10.1186/1471-2407-14-342
Xiao F, Kim YC, Snyder C, Wen H, Chen PX, Luo J et al. Genome instability in blood cells of a BRCA1+ breast cancer family. BMC Cancer. 2014 May 19;14(1). 342. https://doi.org/10.1186/1471-2407-14-342
Xiao, Fengxia ; Kim, Yeong C. ; Snyder, Carrie ; Wen, Hongxiu ; Chen, Pei X. ; Luo, Jiangtao ; Becirovic, Dina ; Downs, Bradley ; Cowan, Kenneth H. ; Lynch, Henry T. ; Wang, San M. / Genome instability in blood cells of a BRCA1+ breast cancer family. In: BMC Cancer. 2014 ; Vol. 14, No. 1.
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