The idea that a mutation in a single gene could lead to a high risk of breast or ovarian
cancer used to be a radical idea. It was not until 1990 that Dr. Mary Claire King
and her team localized a gene for hereditary breast cancer to chromosome 17q21 [
[1]
], which she named BRCA1. This discovery set off a race involving multiple research labs around the globe
to clone and sequence the gene, ultimately ending in 1994 when a team led by Mark
Skolnick became the first to do so [
[2]
,
[3]
]. Skolnick went on to found Myriad genetics, which then acquired a patent for the
sequence of BRCA1, followed shortly the next year with a patent for BRCA2. Due to the patents, from 1996 to 2013, one company provided all commercial sequencing
in the United States for BRCA1 and BRCA2, using PCR amplification and Sanger sequencing. Sanger sequencing will detect small
insertions, deletions, and single base pair changes, but not larger genomic rearrangements,
which represent around 10% of BRCA1 and BRCA2 mutations [
[4]
]. Genomic rearrangement testing in the United States became available commercially
in 2006 as a separate test, and was made part of the BRCA1 and BRCA2 sequencing test in 2013. Next generation sequencing technology was developed in the
late 2000's, allowing for massively parallel sequencing of multiple genes at once
with substantially lower costs [
[5]
], but due to gene patents, panels that included BRCA1 or BRCA2 could not be offered, which limited the clinical use of such testing.- Walsh T.
- Lee M.K.
- Casadei S.
- Thornton A.M.
- Stray S.M.
- Pennil C.
- Nord A.S.
- Mandell J.B.
- Swisher E.M.
- King M.C.
Detection of inherited mutations for breast and ovarian cancer using genomic capture
and massively parallel sequencing.
Proc. Natl. Acad. Sci. U. S. A. 2010; 107 (PMCID: 2906584): 12629-12633
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Article info
Publication history
Published online: December 08, 2018
Footnotes
☆This work was supported by The Liz Tilberis Early Career Award from the Ovarian Cancer Research Alliance, and the Stand Up to Cancer - Ovarian Cancer Research Alliance - National Ovarian Cancer Coalition Dream Team Translational Research Grant (SU2C-AACR-DT16-15)
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© 2018 Elsevier Inc. All rights reserved.
