The BRCA1 Gene

DNA damage resulting in multiple broken chromosomes.[38]

BRCA1 is a human *tumor suppressor gene[1][2][3]; its protein, BRCA1 is involved in the repair of DNA double-strand breaks.[1][4][5][6][7][8] 

*A tumor suppressor gene is a gene that protects a cell from one step on the path to cancer. When this gene mutates to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.[36][37]

The human BRCA1 gene is located on the
long (q) arm of chromosome 17 at region
2 band 1, from base pair 41,196,312 to
base pair 41,277,500.[1][9] 

The DNA double-strand repair mechanism that BRCA1 participates in is homologous recombination.[1] 

During homologous recombination, repair proteins utilize either the homologous intact sequence from a sister chromatid, or that from the same chromosome as a template, depending on cell cycle phase.[1][10][11][12] 

The following statistics (current as of today) are from  The National Cancer Institute's website:[13]

Breast cancer: About 12% of women in the general population will develop breast cancer sometime during their lives.[14]  By contrast, according to the most recent estimates, 55 - 65% of women who inherit a harmful BRCA1 mutation and around 45% of women who inherit a harmful BRCA2 mutation will develop breast cancer by age 70 years.[15][16] 

Ovarian cancer: About 1.4% of women in the general population will develop ovarian cancer sometime during their lives.[14]  By contrast, according to the most recent estimates, 39% of women who inherit a harmful BRCA1 mutation [15][16] and 11 to 17 percent of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by age 70 years.[15][16]

***

*A germ line is the sex cells (ova/egg and sperm) that are used by sexually reproducing organisms to pass on genes from generation to generation. Ova/egg and sperm cells are called germ cells, in contrast to the other cells of the body that are called somatic cells.[34] 

Although about 1 million oocytes are present at birth in the human ovary, only about 500 of these ovulate, and the rest are wasted.[1] 

Women with a *germ line BRCA1 mutation appear to have a diminished oocyte reserve and decreased fertility compared to normally aging women.[1][20][21][22]

All germ line BRCA1 mutations identified to date have been inherited, suggesting the possibility of a large ‘founder effect’ in which a certain mutation is common to a well-defined population group and can, in theory, be traced back to a common ancestor.[1]

An example of a 'founder effect' is seen among Ashkenazi Jews.[1]  

Three mutations in BRCA1 have been reported to account for the majority of Ashkenazi Jewish patients with inherited BRCA1-related breast and/or ovarian cancer: 185delAG, 188del11 and 5382insC in the BRCA1 gene.[17][18][19] (There are similar examples within at least 22 other populations.)

***

For patients with BRCA1 and BRCA2 mutations, methods to diagnose the likelihood of getting cancer were covered by patents owned or controlled by Myriad Genetics.[1][23][24] 

Myriad's business model of offering the diagnostic test exclusively, led to controversy over high prices and the inability to get second opinions from other diagnostic labs, which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit.[1][25][26][27][28][29][30]

In June of 2013, the US Supreme Court ruled unanimously that:[1][31][35]

"A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated." 

Thus, invalidating Myriad's patents on the BRCA1 and BRCA2 genes. However, the Court also held that manipulation of a gene to create something not found in nature could still be eligible for patent protection.[1][31]  

Association for Molecular Pathology v. Myriad Genetics, Inc.[35]
Supreme Court of the United States
Argued April 15, 2013 Decided June 13, 2013
Full case name	Association for Molecular Pathology, et al. v. Myriad Genetics, Inc., et al.
Docket nos.	12-398
Citations	569 U.S. ___ (more)
Prior history	The District Court for the Southern District of New Yorkfound that patents were ineligible. 702 F.Supp. 2d 181, 192–211 (SDNY 2010). On appeal, the Federal Circuitreversed the decision and found 2-1 in favor of Myriad (689 F.3d 1303).
Holding
Naturally occurring DNA sequences, even when isolated from the body, cannot be patented, but artificially created DNA is patent eligible because it is not naturally occurring.
Court membership
Chief Justice John G. Roberts Associate Justices Antonin Scalia · Anthony Kennedy Clarence Thomas · Ruth Bader Ginsburg Stephen Breyer · Samuel Alito Sonia Sotomayor · Elena Kagan
Case opinions
Majority	Thomas, joined by Roberts, Kennedy, Ginsburg, Breyer, Alito, Sotomayor, Kagan, Scalia (in part)
Concurrence	Scalia (all but part I-A)
Laws applied
U.S. Const. Article I, Section 8, Clause 8, 35 U.S.C. § 101

The Federal Court of Australia came to the opposite conclusion, upholding the validity of an Australian Myriad Genetics patent over the BRCA1 gene in February 2013.[1][32] The Federal Court also rejected an appeal in September 2014.[1][33]

The Myriad patents began to expire in 2014.[1]

***

Fin

Updates / Related

BRCA gene mutations and ovarian cancer: an interview with Dr Matulonis, Harvard Medical School / news-medical.net / August 3, 2015

References:

[1] http://en.wikipedia.org/wiki/BRCA1

[2] Duncan JA, Reeves JR, Cooke TG (October 1998). "BRCA1 and BRCA2 proteins: roles in health and disease". Molecular pathology : MP 51 (5): 237–47.doi:10.1136/mp.51.5.237. PMC 395646. PMID 10193517.

[3] Yoshida K, Miki Y (November 2004). "Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage". Cancer science 95 (11): 866–71. doi:10.1111/j.1349-7006.2004.tb02195.x. PMID 15546503.

[4] Check W (2006-09-01). "BRCA: What we know now". College of American Pathologists. Retrieved 2010-08-23.

[5] Friedenson B (August 2007). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer 7: 152–162. doi:10.1186/1471-2407-7-152. PMC 1959234. PMID 17683622.

[6] Friedenson B (2008-06-08). "Breast cancer genes protect against some leukemias and lymphomas" (video). SciVee.

[7]  "Breast and Ovarian Cancer Genetic Screening". Palo Alto Medical Foundation.Archived from the original on 4 October 2008. Retrieved 2008-10-11.

[8] Friedenson B (2007). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer 7: 152. doi:10.1186/1471-2407-7-152. PMC 1959234. PMID 17683622.

[9] National Center for Biotechnology Information, U.S. National Library of MedicineEntrezGene reference information for BRCA1 breast cancer 1, early onset (Homo sapiens)

[10] Kimball's Biologh Pages

[11] Friedenson B (November 2011). "A common environmental carcinogen unduly affects carriers of cancer mutations: carriers of genetic mutations in a specific protective response are more susceptible to an environmental carcinogen". Med. Hypotheses 77 (5): 791–7.doi:10.1016/j.mehy.2011.07.039. PMID 21839586.

[12] Ridpath JR, Nakamura A, Tano K, Luke AM, Sonoda E, Arakawa H, Buerstedde JM, Gillespie DA, Sale JE, Yamazoe M, Bishop DK, Takata M, Takeda S, Watanabe M, Swenberg JA, Nakamura J (December 2007). "Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde". Cancer Res. 67 (23): 11117–22.doi:10.1158/0008-5472.CAN-07-3028. PMID 18056434.

[13] http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA

[14] Howlader N, Noone AM, Krapcho M, et al. (eds.). (2013) SEER Cancer Statistics Review, 1975-2010. Bethesda, MD: National Cancer Institute. Retrieved June 24, 2013.
[15] Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: A combined analysis of 22 studies. American Journal of Human Genetics 2003; 72(5):1117–1130.[PubMed Abstract]
[16] Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. Journal of Clinical Oncology 2007; 25(11):1329–1333. [PubMed Abstract]

[17] Struewing JP, Abeliovich D, Peretz T, Avishai N, Kaback MM, Collins FS, Brody LC (1978). "Isolation of two human tumor epithelial cell lines from solid breast carcinomas".Journal of the National Cancer Institute 61 (2): 967–978. doi:10.1038/ng1095-198.PMID 7550349.

[18] Tonin P, Serova O, Lenoir G, Lynch H, Durocher F, Simard J, Morgan K, Narod S (1995). "BRCA1 mutations in Ashkenazi Jewish women". American Journal of Human Genetics 57 (1): 189. PMC 1801236. PMID 7611288.

[19] Narod SA, Foulkes WD (2004). "BRCA1 and BRCA2: 1994 and beyond". Nature Reviews Cancer 4 (9): 665–676. doi:10.1038/nrc1431. PMID 15343273.

[20] Oktay K, Kim JY, Barad D, Babayev SN (January 2010). "Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks". J. Clin. Oncol. 28 (2): 240–4.doi:10.1200/JCO.2009.24.2057. PMC 3040011. PMID 19996028.

[21] Rzepka-Górska I, Tarnowski B, Chudecka-Głaz A, Górski B, Zielińska D, Tołoczko-Grabarek A (November 2006). "Premature menopause in patients with BRCA1 gene mutation". Breast Cancer Res. Treat. 100 (1): 59–63. doi:10.1007/s10549-006-9220-1.PMID 16773440.

[22] Titus S, Li F, Stobezki R, Akula K, Unsal E, Jeong K, Dickler M, Robson M, Moy F, Goswami S, Oktay K (February 2013). "Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans". Sci Transl Med 5 (172): 172ra21.doi:10.1126/scitranslmed.3004925. PMID 23408054.

[23] US patent 5747282, Skolnick HS, Goldgar DE, Miki Y, Swenson J, Kamb A, Harshman KD, Shattuck-Eidens DM, Tavtigian SV, Wiseman RW, Futreal PA, "7Q-linked breast and ovarian cancer susceptibility gene", issued 1998-05-05, assigned to Myriad Genetics, Inc., The United States of America as represented by the Secretary of Health and Human Services, and University of Utah Research Foundation

[24] US patent 5837492, Tavtigian SV, Kamb A, Simard J, Couch F, Rommens JM, Weber BL, "Chromosome 13-linked breast cancer susceptibility gene", issued 1998-11-17, assigned to Myriad Genetics, Inc., Endo Recherche, Inc., HSC Research & Development Limited Partnership, Trustees of the University of Pennsylvaina

[25]  Myriad Investor Page—see "Myriad at a glance" accessed October 2012

[26] Schwartz J (2009-05-12). "Cancer Patients Challenge the Patenting of a Gene".Health. New York Times.

[27] Robert Cook-Deegan, MD et al (2010) Impact of Gene Patents and Licensing Practices on Access to Genetic Testing for Inherited Susceptibility to Cancer: Comparing Breast and Ovarian Cancers to Colon Cancers: Patents and Licensing for Breast, Ovarian and Colon Cancer Testing Genet Med.12(4 Suppl): S15–S38.

[28] Benowitz S (January 2003). "European groups oppose Myriad's latest patent on BRCA1".J. Natl. Cancer Inst. 95 (1): 8–9. doi:10.1093/jnci/95.1.8. PMID 12509391.

[29] Conley J, Vorhous D, Cook-Deegan J (2011-03-01). "How Will Myriad Respond to the Next Generation of BRCA Testing?". Robinson, Bradshaw, and Hinson. Retrieved2012-12-09.

[30]  "Genetics and Patenting". Human Genome Project Information. U.S. Department of Energy Genome Programs. 2010-07-07.

[31] Liptak, Adam (June 13, 2013). "Supreme Court Rules Human Genes May Not Be Patented". New York Times. 

[32] Corderoy, Amy (February 15, 2013). "Landmark patent ruling over breast cancer gene BRCA1". Sydney Morning Herald. Retrieved June 14, 2013.

[33]  "Australian federal court rules isolated genetic material can be patented". The Guardian. 5 September 2014. Retrieved 14 September 2014.

[34] http://ghr.nlm.nih.gov/glossary=germline

[35] http://en.wikipedia.org/wiki/Association_for_Molecular_Pathology_v._Myriad_Genetics
[36] http://en.wikipedia.org/wiki/Tumor_suppressor_gene
[37] Weinberg, Robert A (2014). "The Biology of Cancer." Garland Science, page 231.

[38] http://en.wikipedia.org/wiki/DNA_repair

Image Credits:

"BRCA1 en" by Kuebi = Armin Kübelbeck - self-made with Inkscape. Derived from SVG-Masterfile.. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:BRCA1_en.png#mediaviewer/File:BRCA1_en.png

"Brokechromo". Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Brokechromo.jpg#mediaviewer/File:Brokechromo.jpg