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Breast tumors : an overview

Written1999-01Daniel Birnbaum, Francois Eisinger, Jocelyne Jacquemier, Michel Longy,Hagay Sobol, Charles Theillet
Laboratoire d'Oncologie Moléculaire, U.119 Inserm, Institut de Cancérologie et d'Immunologie de Marseille, 27 Bd. Le Roure, 13009 Marseille, France
Updated2005-05Maria Luisa Carcangiu, Patrizia Casalini, Sylvie Ménard
Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milano, Italy

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C500-C506,C508-C509 BREAST
Atlas_Id 5018
Phylum Female organs:Breast tumors:an overview

Classification

    Benign epithelial lesions with no significant tendency to malignant transformation include :
  • adenoma:
      • ductal
      • lactating
      • tubular
  • adenosis:
      • apocrine
      • blunt duct
      • microglandular
      • sclerosing
  • fibroadenoma
  • radial scar/complex sclerosing lesions
  • Invasive breast carcinomas are divided into two major categories on the basis of their cytoarchitectural features:

  • Invasive ductal carcinoma :
      • acinic cell carcinoma
      • adenoid cystic carcinoma
      • apocrine carcinoma
      • cribriform carcinoma
      • glycogen-rich/clear cell
      • inflammatory carcinoma
      • lipid-rich carcinoma
      • medullary carcinoma
      • metaplastic carcinoma
      • micropapillary carcinoma
      • mucinous carcinoma
      • neuroendocrine carcinoma
      • oncocytic carcinoma
      • papillary carcinoma
      • sebaceous carcinoma
      • Secretory Breast Carcinoma
      • tubular carcinoma
  • lobular carcinoma
      • pleomorphic
      • signet ring cell

    The recognized precursor lesions of invasive breast carcinoma are :

  • intraductal proliferative lesions:
      • atypical ductal hyperplasia
      • ductal carcinoma in situ
      • florid
      • usual
  • lobular neoplasia/atypical lobular
  • The terminology Invasive ductal/lobular carcinoma does not imply an origin form ducts and lobules, respectively, but the presence of cytoarchitectural and phenotypical features of ductal-type and lobular-type, respectively.
    Ductal adenocarcinoma is the most common.
    Lobular carcinoma is the second malignant breast tumour.
    Medullary carcinoma is rare.
    Hyperplasia is a proliferation without criteria of malignancy.
    Fibroadenomas are benign breast tumours.

    Clinics and Pathology

    Etiology The etiology is multifactorial. It involves diet, genetic and reproductive factors, and related hormone imbalances.
    Epidemiology The annual incidence of breast cancer is about 43/100 000 per year in France, and the mortality rate is about 18/100 000 per year. Invasive breast cancer is the most common carcinoma in women, accounting for 22% of all female cancers. One million women worldwide are diagnosed with breast cancer every year.
    The main factors of risk are:
  • gender : women's risk for the development of invasive breast carcinoma is approximately 400 times that of men.
  • age : breast cancer incidence increases rapidly with age. The mean age at diagnosis is around 60 yrs
  • genetic factors : rare (3 to 5% of cancers and 1/500-800 women) but highly predictive of the disease.
    The areas of higher risk are the affluent populations of North America, Europa and Australia, where 6% of women develop invasive breast carcinoma before age 75.
  • Pathology
  • The most common histologic type of invasive breast carcinoma is designated as ductal, NOS (not otherwise specified). It comprises about 80% of all cases. It is a proliferation of epithelial cells from galactophoral ducts; it may be preceded and accompanied by an in situ component characterized by a proliferation of cells within the ducts without interuption of the basal membrane; when this membrane is altered, the carcinoma is invasive. It can be graded on the basis of the architecture (amount of tubule formations), nuclear atypia and mitotic activity. The score resulting from the sum of these criteria (Nottingham's score) has been show to be an important prognostic indicator. A 3-grade system has been developed for in situ ductal carcinoma. Grade III in situ ductal carcinoma corresponds to the classic comedocarcinoma, whereas Grade I in situ ductal carcinoma merges with atypical ductal hyperplasia, to the point that some authors regard the two process as one and the same. Recently, a proposal has been made to embrace all of the various types of intraductal proliferative lesions under the term ductal intraepithelial neoplasia (DIN) and to divide this into 3 grades, having increasingly higher risk for the development of invasive carcinoma.

    Many morphologic variants of invasive ductal carcinoma exist, some of them extremely rare. They include: tubular, cribriform, medullary, mucinous, neuroendocrine, papillary, micropapillary, apocrine, metaplastic, lipid-rich, secretory, oncocytic, adenoid cystic, acinic cell, glycogen-rich (clear cell), sebaceous, and inflammatory carcinoma. The prognosis of these subtypes varies, some of them having a better and some a worse outcome than invasive ductal carcinoma, NOS.

  • Invasive lobular carcinoma is the second major type (5-10%) of breast cancer. Like its ductal counterpart, it may be preceded or accompanied by an in situ component. It is histologically more homogeneous than ductal carcinoma, but some morphologic variation exist, such as pleomorphic and signet ring cell.
  • Medullary carcinoma, already mentioned above as a rare subtype of invasive ductal carcinoma (1%) with a better prognosis, it has a very distinctive form: sharply circumscribed, accompanied by a heavy lymphoid infiltrate, of high nuclear grade, with a syncytial pattern of growth, and lacking in situ or microglandular features. When one of these features is lacking, the tumor is referred to as atypical medullary carcinoma. A high frequency of medullary carcinoma has been reported in patients with BRCA1 germ line mutation.
  • The different steps in the progression of breast cancer are not well individualized.
  • Hyperplasia is a proliferation of ductal or lobular epithelial cells, without criteria of malignancy; in contrast, atypical hyperplasia has incomplete malignant features and can be difficult to distinguish from in situ carcinoma.
  • Fibroadenomas are the most common form of benign breast tumors.

    These different forms of breast cancer may occur with (hereditary or familial forms) or without (sporadic forms) a familial background.

  • Prognosis There are over 100 factors that have been identified as having prognostic significance in breast carcinoma , but only a minority of them will retain this property when subjected to a multivariate analysis. The most important prognostic factors are: presence and number of positive lymph nodes; tumor size; microscopic grade; and presence of lymphovascular invasion. Other parameters examined pathologically - such as hormone receptors and ERBB2/Neu - have more of a predictive than a prognostic value, in the sense of anticipating a certain type of response to specific forms of therapy. Upon diagnosis, the different presentations are classified upon morphological study, and the gravity and prognosis of the disease is estimated with several parameters that are :
  • tumor size,
  • tumor grade: it is calculated from assessment of tubular differentiation, number of mitoses, and nuclear polymorphism,
  • the absence of estrogen and progesterone receptors,
  • the presence of lymph node metastasis,
  • peritumoral vascular invasion. Other parameters such as the proliferating index (Ki 67, S-phase), the ploidy, and the presence of P53 or ERBB2 alteration may also be useful for prognostic evaluation or as predictive factors for therapeutic response.
  • Genetics

    Note Familial breast cancers are thought to represent about 5 to 10% of all breast cancers.

    Cytogenetics

    Cytogenetics
    Morphological
    Many of the chromosomal aberrations observed in breast carcinomas are not specific of this type of tumour; karyotypes of breast tumours frequently show multiclonality, suggesting the existence of a high degree of intratumoural heterogeneity.

    Alterations of chromosome arms 1q, 3p, 6q, 8p are often present; i(1q) and der t(1;16) are frequent as sole anomalies; +7, +8 and +20 are also frequent; cytogenetic signs of DNA amplification, such as homogeneously staining regions (HSR), are commonly observed in breast carcinomas and seem preferentially associated to 8p.

    Cytogenetics Molecular LOH studies : loss of heterozygosity (LOH) has been associated with physical deletion of large genomic segments containing tumour suppressor genes; common regions of LOH in breast cancer are located on several chromosomes: 1p, 1q, 3p, 6q, 8p, 11q, 13q, 16q, 17p, 17q; almost all breast tumours show LOH in one or several regions; some regions are lost in more than 50% of tumors: 8p, 16q, 17p; precancerous lesions also show LOH.

    CGH : Comparative genomic hybridization (CGH) is a molecular cytogenetics method designed to detect and map chromosomal regions showing abnormal copy numbers in tumors; theoretically, it is possible to detect equally copy number gains (DNA amplification or polyploidies) or losses using this approach; it appears, however, that CGH has a greater sensitivity for gains than for losses; this could be related to the fact that gains are generally of higher magnitude than losses and that losses can be obscured by intratumoral heterogeneity;
    Overall CGH data show that breast tumor genomes undergo severe rearrangements; on average, breast tumors show 5-7 copy number changes/tumor; less than 10% of the tumors analyzed by CGH show neither gains nor losses; almost every chromosome presents at least one site with aberrant copy numbers, however, gains or losses are not evenly distributed throughout the genome.

    Hot spots for gains are routinely observed at 1q (50-55% of the tumors), 8q (60%), 17q (25-30%), 20q (20-25%); gains generally involve subregions of each chromosomal arm and most prevalent regions are 1q31-q32, 8q12 and 8q24 (with MYC and other genes), 17q12 (ERBB2) and 17q23-q24, and 20q13; other regions of recurrent gains are 11q13 (20%, with CCND1), 8p12 (10-15%, and FGFR1), 16p (10-15%); recurrent losses are observed at 1p, 6q, 8p, 11q23-qter, 13q, 16q, 17p and 22q

    CGH has revealed that copy number gains are common in breast tumors and involve 26 (!) chromosomal arms; these data somewhat contradict karyotypical analysis and LOH studies which indicate that losses are more frequent that gains; furthermore, it appears from CGH data that the number of events (gains and losses) increases in advanced cancer.

    Genes involved and Proteins

    Gene Name HRAS
    Location 11p15.5

    Gene Name KRAS
    Location 12p12.1

    Gene Name NRAS
    Location 1p13.2
    Protein H, K, and NRAS genes are a subfamily of the huge RAS/RHO/RAB superfamily and encode ubiquitous cytoplasmic GTP binding p21 proteins involved in signal transduction.
    Somatic mutation RAS genes are mutated at codons 12, 13 and 61in different types of cancers; the frequency of mutations in breast cancer is rather low (<10%) compared to colorectal cancer or pancreatic cancer for instance.

    Gene Name TP53
    Location 17p13
    Dna / Rna 11 exons
    Protein The tumor suppressor gene P53 encodes an ubiquitous nuclear protein involved in the control of genome integrity by preventing cells from dividing before DNA damage is repaired; it has 5 conserved regions containing a transactivation domain, a DNA-binding domain, a tetramerization domain.
    Somatic mutation
  • 20-25% of breast cancers show P53 mutations and these correspond to aggressive breast tumors (loss of estrogen receptor expression).
  • 90% of P53 mutations are found within exons 5 through 9, portions correspondig to codons 165-185 (exon 5) and 235-252 (exon 7) concentrating 50% of the mutations (mutational hot spots); most frequently involved are codons 175, 248 and 273; mutations affecting residues 165-185 and 235-252 bear worse prognostic significance than others; these amino acid residues are located in the L2 and L3 domains of the p53 protein; both these domains bind a Zinc atom and convey contact to DNA; it may thus be of greater phenotypic significance.
  • The majority of P53 mutations (80%) in breast cancer are missense, while nonsense mutations, deletions, insertions or, splice site mutations, which result in the truncation of the protein, make the rest (20%). Prolonged half-life of the protein can also be detected by immunohistochemistry and shows correlation with missense mutations.

  • Gene Name ERBB2
    Location 17q21.2
    Protein The ERBB2 (also called HER2 or NEU) gene encodes an integral type I protein of 185 kDa with a cysteine-rich extracellular region, a transmembrane domain and an intracellular region endowed with a tyrosine kinase activity.
    Somatic mutation HER2 somatic mutations are reported in lung cancer, glioblastoma and ovarian tumor. No somatic mutations in human breast carcinoma are described.
    Amplification : the ERBB2 gene is amplified and overexpressed in 20-25% of breast tumors; tumors showing ERBB2 amplification have predominantly lost estrogen receptor expression (ER-) and are of ductal invasive type; interestingly, 70% of intraductal comedo carcinomas show ERBB2 expression, suggesting a role of this gene in the etiology of this breast tumor subtype ;
    Although ERBB2 amplification and overexpression are related to a worsened course of the disease, they do not represent independent prognostic indicators;
    However, the p185-ERBB2 protein being a transmembrane receptor with low levels of expression in normal tissues has turned out to be a very interesting target for therapeutical approaches; several protocols using engineered anti-ERBB2 antibodies have shown a good success rate.

    Gene Name CCND1
    Location 11q13.3
    Protein The CCND1 gene codes for a cell cycle protein specifically acting in the G1 phase; upon interaction with cyclin dependent kinases (CDK4 or CDK6) cyclin D1 phosphorylates the p105-RB protein and thereby promotes progression in late G1 thus favoring entry into S phase; ectopic overexpression of CCND1 has been shown to result in shortened G1 phase and increased genetic instability, possibly due to a bypass of cell cycle checkpoints.
    Somatic mutation Amplification : the CCND1 gene is amplified in approximately 15% breast cancers; CCND1 amplification is strongly correlated to expression of ER and is prevalent in invasive lobular carcinomas; univariate analysis and Cox model studies show that CCND1 amplification is an independent prognostic factor, however, it bears greatest significance in node positive patients.

    Gene Name FGFR1
    Location 8p11-12
    Protein The FGFR1 gene encodes an integral type I protein of 145 kDa with an extracellular region made of three immunoglobulin-like domains, a transmembrane domain and an intracellular region endowed with a tyrosine kinase activity; alternative splicing create a large number of isoforms; it is a receptor for different members of the fibroblast growth factor family (FGF), which has about 20 members known to date.
    Somatic mutation Amplification : the 8p11-12 region is amplified in about 10% of breast carcinomas; the FGFR1 gene is overexpressed as a consequence of the amplification, and is a good candidate for being the driver gene of the 8p11-12 amplicon; FGFR1 is frequently amplified concomitantly with CCND1 (40% of FGFR1 amplified tumors also show CCND1 amplification); this coamplification of FGFR1 and CCND1 chromosomal regions results in the formation of a hybrid chromosomal structure in which amplified FGFR1 and CCND1 sequences are sequentially arranged.

    Gene Name BRCA1
    Location 17q21
    Dna / Rna Large gene of 22 coding exons spaning more than 70 kb of genomic DNA; exon 11 corresponds to almost 50% of the total coding sequence (5592 nucleotides); the BRCA1 mRNA has a size of 7.8 kb, and a complex pattern of alternative splicing has been reported; it is expressed in numerous tissues (breast, ovary, testis, spleen, thymus ...).
    Protein the corresponding protein has 1863 amino acids, and 190-220 kDa; BRCA1 is not a member of any known gene family; there is only two stretches of evolutionary conserved sequences between humans and mice: at the N-terminus (the RING finger motif), and at the C-terminus (the BRCT domain); the function of BRCA1 is still unknown but it seems to act as a tumor suppressor gene with transcriptional activity; it is involved in cell proliferation processes of mammary epithelial cells in response to hormonal stimulation, in apoptosis, control of recombination and genome integrity after binding to proteins involved in these activities.
    Germinal mutation more than 300 sequence variations at the germline level have been reported; a list is available on the BIC website:

    the germline mutations are dispersed throughout the coding sequence; although a majority of these variations are unique, recurrent mutations such as 185delAG and 5382insC are observed; they were initially described in the Ashkenazy Jewish population; more than 80% of the sequence variants lead to a truncated protein; in contrast, the majority of missense mutations are of unknown clinical significance, excepted those in the RING finger region; in the BRCA1 families, an excess of breast, ovarian, and prostate cancers are seen; all mutations combined, penetrance at age 70 years works out at 56% to 87% in the case of breast cancer, and 16% to 63% in that of ovarian cancer

    BRCA1-associated breast cancers have specific morphological features; they are more frequently of histoprognostic grade 3, highly proliferating and poorly differentiated tumors with a very pleomorphotic nuclear pattern; high frequencies of P53 alterations and negativity of steroid receptors are found in these tumors; a high rate of medullary breast carcinomas is observed among BRCA1-associated breast cancers; evidence for possible genotype-phenotype correlations have been provided concerning the tumor spectrum (breast/ovarian cancer incidence rate), the penetrance, and the proliferation rate of tumors

    Somatic mutation in contrast, somatic mutations of BRCA1 coding sequence are rare in breast/ovarian cancers

    Gene Name BRCA2
    Location 13q12-13
    Dna / Rna like BRCA1 it is a large gene spanning more than 70 kb of genomic DNA; the coding sequence comprises 26 exons (10254 nucleotides) with three large ones (exons 10, 11, 27); the mRNA is of 11-12 Kb long; like BRCA1, it is expressed in various tissues.
    Protein The coresponding protein has 3418 amino acid residues (384 kDa), and is poorly conserved, exepted for the BRC repeats region in exon 11 (8 copies of 20-30 aa); like BRCA1, its function remains unknown; however, it acts as a tumor suppressor gene; transcriptional activation properties have been reported as well as involvement in the DNA repair system.
    Germinal mutation more than 100 unique germ-line mutations are reported and are dispersed throughout the coding sequence (cf the BIC website, address above); recurrent mutations are seen: 6174delT (of Ashkenazy Jewish origin), 999del5 (Icelandic), and 6503delTT (in France and in the UK); the majority lead to a truncated protein and are considered as disease-associated mutations, except for a polymorphic stop codon in exon 27; missense mutations are of uncertain clinical significance

    BRCA2 germline mutations are associated with a high risk of male and female breast cancer; initially, the breast cancer risk was considered as equivalent to that of BRCA1, but in a recent work based only on the Icelandic recurrent BRCA2 999del5 mutation, the estimated risk of breast cancer at age 70 years is considered of only 37%; the ovarian cancer risk is lower than that of BRCA1; in addition, an excess of prostate and pancreas cancers is also seen

    at the morphological level, BRCA2 breast cancers seem to be different from both BRCA1-associated breast cancers and sporadic cases, with a poor differentiation but no high proliferation rate; evidence for possible genotype-phenotype correlation has been provided concerning the tumor spectrum (breast/ovarian cancer incidence rate)

    Somatic mutation somatic mutations of BRCA2 coding sequence are rare in breast/ovarian cancers.

    Gene Name BRCA3
    Location An important breakthrough in the understanding of breast carcinogenesis came with the identification of the two major genes BRCA1 and BRCA2, correponding to 52% and 32% of hereditary breast cancer families, respectively; however, the germline mutations of these genes do not account for all familial cases; additional genes may be involved.

    One such gene might be located on chromosome arm 8p; a positive linkage has first been found in a small set of French families, and then a lod score of almost 3 was obtained in one German family; in addition, the chromosome 8p12-22 region seems to be frequently involved in breast carcinogenesis as well as in different types od tumors (lung, prostate, ovarian); while the 8p12-22 region remain a strong candidate locus, whole-genome linkage studies are in progress to identify the other gene(s) that predispose to breast cancer.


    Gene Name PTEN
    Location 10q23
    Dna / Rna 9 exons
    Protein The PTEN protein (also called MMAC1) is an evolutionary conserved dual-specificity phosphatase sharing extensive similarity with the cytoskeletal protein tensin; PTEN appears to be a tumor suppressor since biallelic inactivations are observed in several types of tumors; inactivating germline mutations are responsible for a cancer prone syndrome, the Cowden disease (see below); also, PTEN -/- ES cells are highly tumorigenic in syngeneic mice whereas PTEN +/- are not.
    Germinal mutation Heterozygous germline mutations are responsible for the Cowden disease, a cancer prone syndrome with high susceptibility to breast carcinoma, and, to a lesser degree, to thyroid carcinoma; most of the mutations are inactivating mutations, either by leading to protein truncation, or by introducing alterations in the phosphatase catalytic domain; germline mutations are also seen in the Bannayan-Riley-Ruvalcaba syndrome
    Somatic mutation

    In spite of the initial description of PTEN homozygous deletion in two breast tumor xenografts and biallelic inactivation of PTEN in two breast carcinoma cell lines, very few PTEN mutations have been observed in sporadic breast carcinoma (1 described mutation in more than 100 analyzed tumors).


    Gene Name ATM
    Location 11q23
    Dna / Rna The ATM gene covers 150 kb of DNA and is spread over 64 exons. It codes for a 13.000 bp transcript, translated into a 3500 aa protein.
    Protein Nuclear protein showing homology at its carboxy terminus with PI-3 kinase; belongs to a family of DNA damage signaling proteins characterized in either yeast or Drosophila; ATM interacts with the ABL protein and is known to transmit a signal to the P53 protein. ATM activity seems restricted to double strand DNA breaks induced by ionising radiations or radio-mimetics; it is noteworthy that the phenotype of Atm KO mice is very similar to that of ATM patients, but that heterozygous Atm +/- mutant mice do not show an increased incidence of cancer.
    Germinal mutation The ATM gene is the genetic determinant to ataxia telangiectasia, a rare recessive disorder, which among other clinical signs, is characterized by an extreme sensitivity to ionising radiations; it has been hypothesized that ATM could play a role in cancer predisposition because AT patients show a 100 fold increased risk of cancer, particularly hematological malignancies; furthermore, epidemiological studies have suggested that AT heterozygotes were also at increased risk of developing cancer, specially breast cancer in women; this, added to the fact that the ATM gene maps to 11q23, a region frequently affected by losses of heterozygosity, suggested that heterozygous mutations in the ATM gene may favor breast cancer development; ATM heterozygotes have been estimated to represent 1% of the total population. Most mutations reported in ATM kindreds result in the truncation of the protein.

    Gene Name Mismatch
    Note MSH2 (2p21), MLH1 (3p21), PMS1 (2q31-33), PMS2 /GTBP/MSH6 (7p22), MSH3 (5q)
    Protein The proteins encoded by the mismatch repair genes are analogues of the bacteria Mut HLS system which is involved in the reparation of DNA replication errors; their defect leads to genomic instability, the most visible consequence of which is the presence of additional alleles at microsatellite markers; the latter are prone to replication errors; their alteration is a hallmark of genomic instability, also called RER (replication error) or MSI (microsatellite instability) phenotype.
    Somatic mutation Frequencies of genomic instability varies from 0 to 40% in breast cancer, depending on studies; however, mutations of mismatch repair genes are uncommon in breast cancer; thus, the high frequencies observed may be due to unknown genes involved in the control of DNA integrity.

    Gene Name CDH1
    Location 16q22.1
    Somatic mutation Mutations and loss of expression of the E-cadherin gene, located on chromosome arm 16q, is very frequentlly observed in breast lobular carcinomas.

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    Citation

    This paper should be referenced as such :
    Carcangiu, ML ; Casalini, P ; Mnard, S
    Breast tumors: an overview
    Atlas Genet Cytogenet Oncol Haematol. 2005;9(4):331-337.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Tumors/breastID5018.html
    History of this paper:
    Birnbaum, D ; Eisinger, F ; Jacquemier, J ; Longy, M ; Sobol, H ; Theillet, C. Breast tumors: an overview. Atlas Genet Cytogenet Oncol Haematol. 1999;3(2):95-100.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37518/01-1999-breastID5018.pdf


    Other genes implicated (Data extracted from papers in the Atlas) [ 732 ]

    Genes AAMP ABCC10 ABCC11 ABL1 ACHE ACLY ACTN4 ACVR1 ADAM10
    ADAM17 ADAM23 ADAM9 ADAMTS12 ADAMTS15 ADAMTS1 ADCYAP1 ADIPOR1 AFP AIFM1
    AIP AKR1C3 AKT1 AKT3 ALOX12 ALOX15 AMFR AMOT ANG ANKHD1
    ANP32A ANXA1 AREG ARID1A ARNT ASAP1 ATF2 ATF3 ATF5 ATP2B4
    ATP5B ATR AURKA AVEN AXL BAG1 BAP1 BARD1 BAX BCAR1
    BCAS3 BCAS4 CCND1 BCL2L12 BCL2L14 BCL2L1 BCL6 BEX2 BIN1 BIRC6
    BMI1 BMP4 BNIP3L BRCA1 BRCA2 BRMS1 BTRC EMSY TIGAR CAPG
    CARD10 CARD8 CARTPT CASR CAV1 CBFA2T3 CBX7 CCNA1 CCNB1 CCR1
    CCR2 CD151 CD200 CD248 CD44 CD59 CD82 CD9 CDC20 CDC25A
    CDC25A CDC42 CDCP1 CDH13 CDH3 CDK4 CDKN1A CEACAM1 CELF2 CENPF
    AGAP2 CHD5 CHD6 CHFR CHFR CHKA CHST11 CITED2 CITED4 CKS1B
    CKS2 CLDN4 CLDN6 CLDN7 CLIC4 CLSPN CLU COL1A2 COPS2 CPEB4
    CPM CRK CRTC2 CRYAB CSE1L CSF1R CST6 CSTA CSTB CTCF
    CTDSPL CTGF CTHRC1 CTNND1 CTSB CTSH CTSL CUX1 CXCL10 CXCL12
    CXCL17 CXCR1 CXCR3 CXXC5 CYB5A CYP4B1 CYR61 DAB2 DAPK1 DCC
    DDR1 DDX1 DENR DHFR DIABLO DIRAS3 DKK3 DLC1
    DLX2 DLX4 DLX5 DLX6 DMBT1 DNAJA3 DNMT3B DOCK1 DPP4 DUSP1
    DVL1 E2F1 E2F4 EBAG9 ECM1 EDIL3 EEF1A1 EEF1A2 EEF2K EFEMP1
    EGR1 EHMT2 EIF2AK2 EIF3A EIF4EBP1 EIF4E ELAVL1 EMP3 ENAH ENG
    ENO1 ENOX2 ENPP2 EPAS1 EPB41L3 EPHA1 EPHA2 EPHB6 EPS8 ERBB2
    ERBB3 ERCC1 ERRFI1 ERVW-1 ESR2 ESRRA ESRRG ETS1 ETS2 ETV4
    MECOM EYA2 EZH2 FANCA FABP5 FABP7 FANCC FAM107B FAT1 FAU
    FBLN1 FBLN2 FBLN5 FBXO11 FBXO31 FEN1 FGF1 FGF2 FGF8 FGFR1
    FGFR2 FGFR4 FHL2 FKBP5 FOSL1 FOXA1 FOXC1 FOXE1 FOXF1 FOXM1
    FOXM1 FOXP1 FOXP3 FOXQ1 MTOR FRZB FSCN1 FSTL3 FURIN FXYD3
    GAB2 GADD45A GALNT6 GAS5 GATA2 GATA3 GDF15 GLI2 GNA11 GPC1
    GPC3 GPC5 GPNMB GPRC5A GPX1 GPX3 GRB2 GREB1 GRM1
    GRN GRPR GSTA1 GSTM1 H2AFX CCDC6 HACE1 HBP1 HDAC2 HELLS
    HFE HGF HIC1 HIPK2 HLA-G HMGA2 HMGA2 HNRNPD HOXC8 HSPA5
    HSPB1 HSPB8 HSPG2 HTATIP2 HTRA1 HTRA2 HUS1 HYAL2 ICAM1 ID1
    ID4 IDO1 IGF1 IGF1R IGF2BP1 IGF2R IL17A IL1B IL1RN IL23A
    IL6 IL7R ILK ING1 ING3 ING4 INGX INPPL1 IRF1 IRS1
    ITGA6 ITGA9 JAK1 KCNH1 KDR KIAA1524 CCAR2 KIF14 KIT KLF4
    KLF5 KLK10 KLK4 KLK5 KLK7 KLK8 KLLN KRAS LASP1 LATS1
    LATS2 LCK LGALS3 LGI1 LHCGR LIMD1 LIMK1 LOX LOXL2 LOXL3
    LOXL4 LPAR1 LPAR2 ADGRL2 LRIG1 LRP1B LRP5 LZTS1 MACROD1 MAGEA3
    MAL MAP2 MAP2K4 MAP3K7 MAPK12 MAPK1 MAPK3 MAPK7 MCAM MCM3
    MED28 MEG3 MEIS1 MELK MIEN1 MIER1 MIR100 MIR106B MIR107
    MIR122 MIR126 MIR135A1 MIR143 MIR145 MIR146B MIR183 MIR196B MIR200A MIR200B
    MIR200C MIR211 MIR22 MIR26A1 MIR27A MIR30A MIR373 MIR429 MIR744 MIR744
    MIR10B MIR125A MIR125B1 MIR125B2 MIR21 MIR7-1 MKI67 CASC3 STARD3 MME
    MMP14 MMP15 MMP26 MMP2 MMP9 MOAP1 MSH6 MST1 MSX2 MTA3
    MTHFR MTUS1 MUC17 MUC6 MYBBP1A MYB MYBL2 MYC MYEOV MYLK
    NACC1 NAMPT NANOG NAT1 NAT2 NCOA3 NCR2 NDRG1 NDUFA13 NFATC2
    NFKB1 NGFR NME1 NMT1 NOL3 NOTCH1 NOTCH2 NPY1R NPY
    NR0B1 NR3C1 NR3C2 NR4A1 NRCAM NRF1 NRIP1 NT5E NTSR1 NUMB
    OLFM4 OPCML ORAI3 OSGIN1 P2RX7 EP300 TP53 PA2G4 PAEP PAK1
    PAK2 PARK2 PARVB PAWR PAX2 PBRM1 PCNA PCSK6 PDCD4 PDCD6
    PDX1 PEA15 PEBP1 PEG3 PERP PFKFB3 PFKFB4 PHLDA1 PHLPP2 PIK3CA
    PIK3CD PIK3R1 PIP4K2A PIWIL2 PKM PLA2G2A PLAGL1 PLAUR PLCB2 PLCD1
    PLCG1 PLD1 PLD2 PLK1 PLXNB1 PML POU1F1 PPARG PPM1D PPP1R13L
    PPP1R1B PPP1R9B PPP2R1A PRAME PRDM2 PRKCD PRKCI PRLR PRSS8 PRUNE
    PSEN2 PSIP1 PTEN PTEN PTGIS PTHLH PTK2 PTK6 PTK7 PTMA
    PTN PTPN14 PTPN1 PTPN6 PTPRA PTPRJ PTTG1 NECTIN4 PXN PYCARD
    PYY RAB31 RAC3 RAD51D RAD52 RAD9A RAF1 RAN RARRES1 RARRES3
    RASSF1 RASSF2 RASSF5 RASSF6 RBBP7 RBL2 RBM5 RELA REPS2 REST
    RGS2 RHOA RHOBTB1 RHOBTB2 RHOC RNASET2 RND3 RNF11 ROBO1
    ROCK2 MST1R RPRM RPS27 RPS6KA1 RPS6KA6 RRM2 RUNX2 S100A2 S100A4
    S100A7 S100A8 S100A9 S100P SASH1 SATB1 SCAF1 SCD SDC1 SDCBP
    SEMA3B SEMA3F SEP15 SERPINB3 SERPINB5 SFRP4 SGO1 SH3GL2 SH3PXD2A SHBG
    SHC1 SIAH1 SIAH2 STIL SIPA1 SIRT1 SIVA1 SIX1 SLC16A1 SLC16A3
    SLC19A3 SLC1A5 SLC39A6 SLC5A8 SLC9A3R1 SLIT2 SLIT3 SLPI SMAD4
    SMARCA4 SMYD2 SMYD3 SNAI1 SNCG SOCS2 SOX2 SOX4 SPAM1 SPINK1
    SPINT1 SPP1 SPRY1 SRC SRSF1 SRSF3 SRXN1 SSX2 MMP11 ST6GALNAC1
    STARD13 STAT3 STAT5B STEAP1 STK11 STMN1 STOML2 SULF1 SULF2 SYK
    TAC1 TACC1 TACC2 TACC3 EPCAM TAGLN TBX2 TBX3 TEK TERF2
    TET2 TFAP2A TFAP2C TFF1 TFF2 TFF3 TFRC TGFB1 TGFBR2 TGFBR3
    TGM2 THBS1 THBS2 THBS2 THRB THRB THRSP TIAM1 TIMP2 TJP2
    TMSB10 TNC TNFAIP3 TNFRSF11B TNFSF15 TNKS TNN TNS4 TP53BP2 TP53INP1
    TP63 TPD52 TPX2 TRIM27 TRIM37 TRIO TRPM8 TWIST1 TWIST2
    TYMP UBE2C USF1 USP15 USP32 UTS2 VAV3 VCAN VCP VIP
    VRK2 VTCN1 WHSC1L1 WIF1 WISP2 WNT1 WNT5A WRAP53 WWC1
    WWOX WWP1 WWTR1 XRCC3 XRCC5 XRCC6 YAP1 YBX1 YPEL3 ZBTB7A
    ZFP36L1 ZNF217

    External links

    arrayMapTopo ( C50) arrayMap ((UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
     
     
    Other databaseOn-Line Breast Cancer Mutation DataBase
    Other databaseTumor Portal - Broad Institute
    Other databaseICGC Data Portal - [BRCA-UK] Breast Triple Negative/Lobular Cancer - UK
    Other databaseICGC Data Portal - [BRCA-US] Breast Cancer - TCGA, US
    Other databasecBioPortal: Breast Invasive Carcinoma (British Columbia, Nature 2012)
    Other databasecBioPortal: Breast Invasive Carcinoma (Broad, Nature 2012)
    Other databasecBioPortal: Breast Invasive Carcinoma (Sanger, Nature 2012)
    Other databasecBioPortal: Breast Invasive Carcinoma (TCGA, Nature 2012)
    Other databasecBioPortal: Breast Invasive Carcinoma (TCGA, Provisional)
    Other databaseBreast Cancer (My Cancer Genome)
    Other databaseBreast invasive carcinoma (BRCA) TCGA Copy Number Portal
    Other databaseBreast carcinoma ( intOGen )
    Other databaseBreast carcinoma ( intOGen )
    Other databaseBreast carcinoma ( intOGen )
    Other databaseBreast carcinoma ( intOGen )
    Other databaseBreast carcinoma ( intOGen )
    Other databaseBreast carcinoma ( intOGen )
    Other databaseBreast Invasive Carcinoma (TCGA)(OASIS Portal)
    Other databaseBreast Cancer (METABRIC)(OASIS Portal)
    Other databaseBreast Cancer Overview - Disease Synopsis [canSAR]
    Other databaseBreast Invasive Carcinoma [ Genomic Data Commons - NCI TCGA-BRCA]
    Disease databaseBreast tumors : an overview
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed


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    indexed on : Sat Jun 11 13:15:25 CEST 2016


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