The effects of BRCA1 missense variants V1804D and M1628T on transcriptional activity

Kimberly Ostrow, Valerie McGuire, Alice S. Whittemore, Richard A. DiCioccio

Research output: Contribution to journalArticle

Abstract

Many families with multiple cases of ovarian cancer, breast cancer, or both segregate inherited mutations in one allele of the tumor suppressor gene BRCA1. Genetic testing is used to assess cancer risk; however, testing can detect missense DNA alterations, called unclassified variants, of unknown functional and biological significance with uncertain risk implications. Some missense variants at the transcriptional activation domain of BRCA1 of cancer patients inactivate transcriptional activity of BRCA1, providing evidence that they are deleterious. We identified the variants V1804D and M1628T at the transcriptional activation domain of BRCA1 of two ovarian cancer patients without a family history of ovarian or breast cancer. To test if these residues are critical for transcriptional activation, we created V1804D and M1628T independently in BRCA1 cDNA via site-directed mutagenesis in a mammalian expression vector, pcDNA3.1. Wild-type, mutant, and empty vector constructs were tested in human kidney 293 cells using a p53-responsive luciferase reporter. M1628T had the same transcriptional activity as wild-type BRCA1 but V1804D and the empty vector control showed a 60% reduction. This indicates that V1804D is deleterious but M1628T is not.

Original languageEnglish (US)
Pages (from-to)177-180
Number of pages4
JournalCancer Genetics and Cytogenetics
Volume153
Issue number2
DOIs
StatePublished - Sep 2004
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Transcriptional Activation
Breast Neoplasms
Genetic Testing
Site-Directed Mutagenesis
Tumor Suppressor Genes
Luciferases
Neoplasms
Complementary DNA
Alleles
Kidney
Mutation
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

The effects of BRCA1 missense variants V1804D and M1628T on transcriptional activity. / Ostrow, Kimberly; McGuire, Valerie; Whittemore, Alice S.; DiCioccio, Richard A.

In: Cancer Genetics and Cytogenetics, Vol. 153, No. 2, 09.2004, p. 177-180.

Research output: Contribution to journalArticle

Ostrow, Kimberly ; McGuire, Valerie ; Whittemore, Alice S. ; DiCioccio, Richard A. / The effects of BRCA1 missense variants V1804D and M1628T on transcriptional activity. In: Cancer Genetics and Cytogenetics. 2004 ; Vol. 153, No. 2. pp. 177-180.
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