BRCA1

BRCA geneFANCSBABAM1BRCABRCA 1BRCA IBRCA#1BRCA-1BRCA1 (breast cancer type 1 susceptibility protein)BRCA1 gene
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 gene.wikipedia
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BRCA mutation

BRCABRCA'' mutationBRCA1/2
If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer.
A BRCA mutation is a mutation in either of the BRCA1 and BRCA2 genes, which are tumour suppressor genes.

BRCA2

FANCD1breast cancer 2BRCA 2
BRCA1 and BRCA2 are unrelated proteins, but both are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. Methods to test for the likelihood of a patient with mutations in BRCA1 and BRCA2 developing cancer were covered by patents owned or controlled by Myriad Genetics.
BRCA2 and BRCA1 are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA or destroy cells if DNA cannot be repaired.

Breast cancer

breastbreast carcinomabreast cancers
If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. Certain variations of the BRCA1 gene lead to an increased risk for breast cancer as part of a hereditary breast-ovarian cancer syndrome. Breast cancers can be classified based on receptor status or histology, with triple-negative breast cancer (15%–25% of breast cancers), HER2+ (15%–30% of breast cancers), ER+/PR+ (about 70% of breast cancers), and Invasive lobular carcinoma (about 5%–10% of invasive breast cancer).
About 5–10% of cases are due to genes inherited from a person's parents, including BRCA1 and BRCA2 among others.

Myriad Genetics

D'Arcy v Myriad Genetics Inc Myriad Genetics IncMyriad Genetics case
Methods to test for the likelihood of a patient with mutations in BRCA1 and BRCA2 developing cancer were covered by patents owned or controlled by Myriad Genetics.
Myriad's discovery of the breast cancer gene, BRCA1 was universally acclaimed as a monumental achievement: "There is no more exciting story in medical science."

BRCT domain

BRCT
The human BRCA1 protein consists of four major protein domains; the Znf C3HC4- RING domain, the BRCA1 serine domain and two BRCT domains.
It is named after the C-terminal domain of BRCA1, a DNA-repair protein that serves as a marker of breast cancer susceptibility.

Biological patent

gene patentpatentedgenetic patent
Methods to test for the likelihood of a patient with mutations in BRCA1 and BRCA2 developing cancer were covered by patents owned or controlled by Myriad Genetics.
In February 2013, Judge Justice John Nicholas ruled in the Federal Court of Australia in favour of a Myriad Genetics patent on the BRCA1 gene.

RING finger domain

RINGRING fingerRING domain
The human BRCA1 protein consists of four major protein domains; the Znf C3HC4- RING domain, the BRCA1 serine domain and two BRCT domains. This RING domain interacts with associated proteins, including BARD1, which also contains a RING motif, to form a heterodimer.
AMFR, BBAP, BFAR, BIRC2, BIRC3, BIRC7, BIRC8, BMI1, BRAP, BRCA1, CBL, CBLB, CBLC, CBLL1, CHFR, COMMD3, DTX1, DTX2, DTX3, DTX3L, DTX4, DZIP3, HCGV, HLTF, HOIL-1, IRF2BP2, LNX1, LNX2, LONRF1, LONRF2, LONRF3, MARCH1, MARCH10, MARCH2, MARCH3, MARCH4, MARCH5, MARCH6, MARCH7, MARCH8, MARCH9, MDM2, MEX3A, MEX3B, MEX3C, MEX3D, MGRN1, MIB1, MID1, MID2, MKRN1, MKRN2, MKRN3, MKRN4, MNAT1, MYLIP, NFX1, NFX2, PCGF1, PCGF2, PCGF3, PCGF4, PCGF5, PCGF6, PDZRN3, PDZRN4, PEX10, PHRF1, PJA1, PJA2, PML, PML-RAR, PXMP3, RAD18, RAG1, RAPSN, RBCK1, RBX1, RC3H1, RC3H2, RCHY1, RFP2, RFPL1, RFPL2, RFPL3, RFPL4B, RFWD2, RFWD3, RING1, RNF2, RNF4, RNF5, RNF6, RNF7, RNF8, RNF10, RNF11, RNF12, RNF13, RNF14, RNF19A, RNF20, RNF24, RNF25, RNF26, RNF32, RNF38, RNF39, RNF40, RNF41, RNF43, RNF44, RNF55, RNF71, RNF103, RNF111, RNF113A, RNF113B, RNF121, RNF122, RNF123, RNF125, RNF126, RNF128, RNF130, RNF133, RNF135, RNF138, RNF139, RNF141, RNF144A, RNF145, RNF146, RNF148, RNF149, RNF150, RNF151, RNF152, RNF157, RNF165, RNF166, RNF167, RNF168, RNF169, RNF170, RNF175, RNF180, RNF181, RNF182, RNF185, RNF207, RNF213, RNF215, RNFT1, SH3MD4, SH3RF1, SH3RF2, SYVN1, TIF1, TMEM118, TOPORS, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7, TRAIP, TRIM2, TRIM3, TRIM4, TRIM5, TRIM6, TRIM7, TRIM8, TRIM9, TRIM10, TRIM11, TRIM13, TRIM15, TRIM17, TRIM21, TRIM22, TRIM23, TRIM24, TRIM25, TRIM26, TRIM27, TRIM28, TRIM31, TRIM32, TRIM33, TRIM34, TRIM35, TRIM36, TRIM38, TRIM39, TRIM40, TRIM41, TRIM42, TRIM43, TRIM45, TRIM46, TRIM47, TRIM48, TRIM49, TRIM50, TRIM52, TRIM54, TRIM55, TRIM56, TRIM58, TRIM59, TRIM60, TRIM61, TRIM62, TRIM63, TRIM65, TRIM67, TRIM68, TRIM69, TRIM71, TRIM72, TRIM73, TRIM74, TRIML1, TTC3, UHRF1, UHRF2, VPS11, VPS8, ZNF179, ZNF294, ZNF313, ZNF364, ZNF650, ZNFB7, ZNRF1, ZNRF2, ZNRF3, ZNRF4, and ZSWIM2.

Association for Molecular Pathology v. Myriad Genetics, Inc.

Association for Molecular Pathology v. Myriad GeneticsAMP v. Myriad GeneticsAssociation for Molecular Pathology v. U.S. Patent and Trademark Office
Myriad's business model of offering the diagnostic test exclusively led from Myriad being a startup in 1994 to being a publicly traded company with 1200 employees and about $500M in annual revenue in 2012; it also led to controversy over high prices and the inability to obtain second opinions from other diagnostic labs, which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit.
In 1990, at a meeting of the American Society of Human Genetics, a team of scientists led by Mary-Claire King, from the University of California, Berkeley announced the localization through linkage analysis of a gene associated with increased risk for breast cancer (BRCA1) to the long arm of chromosome 17.

Penetrance

incomplete penetrancepenetrantvariable penetrance
The predominant allele has a normal, tumor suppressive function whereas high penetrance mutations in these genes cause a loss of tumor suppressive function which correlates with an increased risk of breast cancer.

ATM serine/threonine kinase

ATMAtaxia telangiectasia mutatedATM kinase
Reported phosphorylation sites of BRCA1 are concentrated in the SCD, where they are phosphorylated by ATM/ATR kinases both in vitro and in vivo.
Several of these targets, including p53, CHK2, BRCA1, NBS1 and H2AX are tumor suppressors.

BARD1

This RING domain interacts with associated proteins, including BARD1, which also contains a RING motif, to form a heterodimer.
Most, if not all, BRCA1 heterodimerizes with BARD1 in vivo.

Ubiquitin

ubiquitinationubiquitylationubiquitinated
Thus, this protein plays a role in transcription, and DNA repair of double-strand DNA breaks ubiquitination, transcriptional regulation as well as other functions.
This K63 chain appears to recruit RAP80, which contains a UIM, and RAP80 then helps localize BRCA1.

Mary-Claire King

Dr. Mary-Claire KingMary Claire KingMary Claire-King
The first evidence for the existence of a gene encoding a DNA repair enzyme involved in breast cancer susceptibility was provided by Mary-Claire King's laboratory at UC Berkeley in 1990.
In 1991 King officially named the gene BRCA1.

Ovarian cancer

ovarianovarian carcinomaovary
In addition to breast cancer, mutations in the BRCA1 gene also increase the risk of ovarian and prostate cancers.
About 10% of cases are related to inherited genetic risk; women with mutations in the genes BRCA1 or BRCA2 have about a 50% chance of developing the disease.

Hereditary breast–ovarian cancer syndrome

hereditary breast-ovarian cancer syndromeHereditary Breast and Ovarian CancerHereditary Breast and Ovarian Cancer syndrome
Certain variations of the BRCA1 gene lead to an increased risk for breast cancer as part of a hereditary breast-ovarian cancer syndrome.
* BRCA mutations: Harmful mutations in the BRCA1 and BRCA2 genes can produce very high rates of breast and ovarian cancer, as well as increased rates of other cancers.

Fanconi anemia

Fanconi anaemiaFanconi's anaemiaFanconi anemia C
Double-strand breaks occur as intermediates after the crosslinks are removed, and indeed, biallelic mutations in BRCA1 have been identified to be responsible for Fanconi Anemia, Complementation Group S, a genetic disease associated with hypersensitivity to DNA crosslinking agents.
Scientists have identified 22 FA or FA-like genes: FANCA, FANCB, FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (BRIP1), FANCL, FANCM, FANCN (PALB2), FANCO (RAD51C), FANCP (SLX4), FANCQ (XPF), FANCS (BRCA1), FANCT (UBE2T), FANCU (XRCC2), FANCV (REV7), and FANCW (RFWD3).

Prostate cancer

prostatehormone-refractory prostate cancermetastatic prostate cancer
In addition to breast cancer, mutations in the BRCA1 gene also increase the risk of ovarian and prostate cancers.
Mutations in BRCA1 and BRCA2, important risk factors for ovarian cancer and breast cancer in women, have also been implicated in prostate cancer.

Triple-negative breast cancer

triple negative breast cancertriple negativeTNBC
Breast cancers can be classified based on receptor status or histology, with triple-negative breast cancer (15%–25% of breast cancers), HER2+ (15%–30% of breast cancers), ER+/PR+ (about 70% of breast cancers), and Invasive lobular carcinoma (about 5%–10% of invasive breast cancer).
Among breast cancer patients, 15–20% of women have been diagnosed as triple-negative, while the majority of TNBC patients have been found to be young women or women with a mutation in the BRCA1 gene.

Tumor suppressor

tumor suppressor genetumor suppressor genestumour suppressor gene
BRCA1 is a human tumor suppressor gene (also known as a caretaker gene) and is responsible for repairing DNA.

Ubiquitin ligase

E3 ubiquitin ligaseE3 ligaseubiquitin ligases
The ring domain is an important element of ubiquitin E3 ligases, which catalyze protein ubiquitination.
E3 ubiquitin ligases regulate homeostasis, cell cycle, and DNA repair pathways, and as a result, a number of these proteins are involved in a variety of cancers, including famously MDM2, BRCA1, and Von Hippel-Lindau tumor suppressor.

RAD51

RAD51 nucleoprotein filament
In the nucleus of many types of normal cells, the BRCA1 protein interacts with RAD51 during repair of DNA double-strand breaks.
Another complex, the BRCA1-PALB2-BRCA2 complex, and the RAD51 paralogs cooperate to load RAD51 onto ssDNA coated with RPA to form the essential recombination intermediate, the RAD51-ssDNA filament.

DNA repair

DNA damagerepairtranslesion synthesis
They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double-strand breaks.
A class of checkpoint mediator proteins including BRCA1, MDC1, and 53BP1 has also been identified.

Transcriptional regulation

regulatetranscription regulationtranscription regulator
Thus, this protein plays a role in transcription, and DNA repair of double-strand DNA breaks ubiquitination, transcriptional regulation as well as other functions.
In breast cancer, transcriptional repression of BRCA1 may occur more frequently by over-expressed microRNA-182 than by hypermethylation of the BRCA1 promoter (see Low expression of BRCA1 in breast and ovarian cancers).

Negative elongation factor

negative elongation factor (NELF)NELFNELF (negative elongation factor)
BRCA1 interacts with the NELF-B (COBRA1) subunit of the NELF complex.
Microsequencing analysis demonstrated that NELF-B was the protein previously identified as the protein encoded by the gene COBRA1, and was shown to interact with BRCA1.

Cancer

cancersmalignanciescancerous
Such mutations and epigenetic alterations may give rise to cancer.
Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer, and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), which is present in about 3% of people with colorectal cancer, among others.