Markers for breast cancer

Abstract

Correlations between polymorphisms and breast cancer are provided. Methods of diagnosing, prognosing, and treating breast cancer are provided. Systems and kits for diagnosis, prognosis and treatment of breast cancer are provided. Methods of identifying breast cancer modulators are also described.

1 . A method of identifying a breast cancer phenotype for an organism or biological sample derived therefrom, the method comprising: 
 detecting, in the organism or biological sample, a polymorphism or a locus closely linked thereto, the polymorphism being selected from a polymorphism of FIGS.  1  or  2 , wherein the polymorphism is associated with a breast cancer phenotype; and,    correlating the polymorphism or locus to the phenotype.    
   
   
       2 . The method of  claim 1 , wherein the organism is a mammal, or the biological sample is derived from a mammal.  
   
   
       3 . The method of  claim 1 , wherein the organism is a human patient, or the biological sample is derived from a human patient.  
   
   
       4 . The method of  claim 1 , wherein the detecting comprises amplifying the polymorphism, linked locus or a sequence associated therewith and detecting the resulting amplicon.  
   
   
       5 . The method of  claim 4 , wherein the amplifying comprises: 
 a) admixing an amplification primer or amplification primer pair with a nucleic acid template isolated from the organism or biological sample, wherein the primer or primer pair is complementary or partially complementary to a region proximal to or including the polymorphism or linked locus, and is capable of initiating nucleic acid polymerization by a polymerase on the nucleic acid template; and,    b) extending the primer or primer pair in a DNA polymerization reaction comprising a polymerase and the template nucleic acid to generate the amplicon.    
   
   
       6 . The method of  claim 4 , wherein the amplicon is detected by a process that includes one or more of: hybridizing the amplicon to an array, digesting the amplicon with a restriction enzyme, or real-time PCR analysis.  
   
   
       7 . The method of  claim 4 , comprising partially or fully sequencing the amplicon.  
   
   
       8 . The method of  claim 4 , wherein the amplifying comprises performing a polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR), or ligase chain reaction (LCR) using nucleic acid isolated from the organism or biological sample as a template in the PCR, RT-PCR, or LCR.  
   
   
       9 . The method of  claim 1 , wherein the polymorphism or linked locus comprises a single nucleotide polymorphism (SNP).  
   
   
       10 . The method of  claim 1 , wherein the polymorphism comprises an allele selected from the group consisting of: alleles in FIGS.  1  or  2 .  
   
   
       11 . The method of  claim 1 , wherein the polymorphism is a single nucleotide polymorphism selected from the group consisting of: SNP ID 2312116, SNP ID 1622530, SNP ID 3712013, SNP ID 1509710, SNP ID 843029, SNP ID 1990126, SNP ID 604819, SNP ID 3025734, SNP ID 1152499, SNP ID 4415909, SNP ID 1732681, SNP ID 4281579, SNP ID 4454457, SNP ID 2616199, SNP ID 1720694, SNP ID 4077723, SNP ID 3711990, SNP ID 3337858, SNP ID 4093095, SNP ID 4213825, SNP ID 3488617, SNP ID 3610210, SNP ID 3451239, SNP ID 1582533, SNP ID 3488150, SNP ID 2770052, SNP ID 4141351, SNP ID 1335030, SNP ID 2211665, and SNP ID 4538418.  
   
   
       12 . The method of  claim 1 , wherein the polymorphism is in a gene or locus selected from the group consisting of: FGFR2, A2BP1, TNRC9, H19, FSTL5, LSP1, LOC388927, UNQ9391, HCN1, LOC441192, TNRC9, NR3C2, KIAA0826, FLJ31033, AACS, FRMD4A and SEC31L2.  
   
   
       13 . The method of  claim 12 , wherein the method comprises detecting a plurality of polymorphisms or linked loci in a plurality of said genes.  
   
   
       14 . The method of  claim 12 , wherein the method comprises detecting at least one polymorphism in each of: FGFR2, A2BP1, TNRC9, H19, and FSTL5.  
   
   
       15 . The method of  claim 12 , wherein the method comprises detecting at least one polymorphism for each of: SNP ID 2312116, SNP ID 1622530, SNP ID 3712013, SNP ID 1509710, and SNP ID 843029.  
   
   
       16 . The method of  claim 12 , wherein the method comprises detecting at least one polymorphism for each of: SNP ID 2312116, SNP ID 1622530, SNP ID 3712013, SNP ID 1509710, SNP ID 843029, SNP ID 1990126, SNP ID 604819, SNP ID 3025734, SNP ID 1152499, SNP ID 4415909, SNP ID 1732681, SNP ID 4281579, SNP ID 4454457, SNP ID 2616199, SNP ID 1720694, SNP ID 4077723, SNP ID 3711990, SNP ID 3337858, SNP ID 4093095, SNP ID 4213825, SNP ID 3488617, SNP ID 3610210, SNP ID 3451239, SNP ID 1582533, SNP ID 3488150, SNP ID 2770052, SNP ID 4141351, SNP ID 1335030, SNP ID 2211665, and SNP ID 4538418, or at least one polymorphism in each of: FGFR2, A2BP1, TNRC9, H19, FSTL5, LSP1, LOC388927, UNQ9391, HCN1, LOC441192, TNRC9, NR3C2, KIAA0826, FLJ31033, AACS, FRMD4A and SEC31L2.  
   
   
       17 . The method of  claim 1 , wherein the linked locus is a closely linked locus that is about 5 cM or less from the polymorphism.  
   
   
       18 . The method of  claim 1 , wherein correlating the polymorphism or linked locus to the breast cancer phenotype comprises referencing a look up table that comprises correlation information for alleles of the polymorphism or linked locus and the breast cancer phenotype.  
   
   
       19 . A composition comprising a plurality of marker probes or amplification primers that detect or amplify a plurality of polymorphisms selected from: SNP ID 2312116, SNP ID 1622530, SNP ID 3712013, SNP ID 1509710, SNP ID 843029, SNP ID 1990126, SNP ID 604819, SNP ID 3025734, SNP ID 1152499, SNP ID 4415909, SNP ID 1732681, SNP ID 4281579, SNP ID 4454457, SNP ID 2616199, SNP ID 1720694, SNP ID 4077723, SNP ID 3711990, SNP ID 3337858, SNP ID 4093095, SNP ID 4213825, SNP ID 3488617, SNP ID 3610210, SNP ID 3451239, SNP ID 1582533, SNP ID 3488150, SNP ID 2770052, SNP ID 4141351, SNP ID 1335030, SNP ID 2211665, and SNP ID 4538418.  
   
   
       20 . The composition of  claim 19 , wherein the marker probes or amplification primers are free in solution.  
   
   
       21 . A method of identifying a modulator of a breast cancer phenotype, the method comprising: 
 contacting a potential modulator to a gene or gene product, wherein the gene or gene product comprises or is closely linked to a polymorphism of selected from SNP ID 2312116, SNP ID 1622530, SNP ID 3712013, SNP ID 1509710, SNP ID 843029, SNP ID 1990126, SNP ID 604819, SNP ID 3025734, SNP ID 1152499, SNP ID 4415909, SNP ID 1732681, SNP ID 4281579, SNP ID 4454457, SNP ID 2616199, SNP ID 1720694, SNP ID 4077723, SNP ID 3711990, SNP ID 3337858, SNP ID 4093095, SNP ID 4213825, SNP ID 3488617, SNP ID 3610210, SNP ID 3451239, SNP ID 1582533, SNP ID 3488150, SNP ID 2770052, SNP ID 4141351, SNP ID 1335030, SNP ID 2211665, and SNP ID4538418; and,    detecting an effect of the potential modulator on the gene or gene product, thereby identifying whether the potential modulator modulates the phenotype.    
   
   
       22 . The method of  claim 21 , wherein the gene or gene product comprises a polymorphism selected from SNP ID 2312116, SNP ID 1622530, SNP ID 3712013, SNP ID 1509710, SNP ID 843029, SNP ID 1990126, SNP ID 604819, SNP ID 3025734, SNP ID 1152499, SNP ID 4415909, SNP ID 1732681, SNP ID 4281579, SNP ID 4454457, SNP ID 2616199, SNP ID 1720694, SNP ID 4077723, SNP ID 3711990, SNP ID 3337858, SNP ID 4093095, SNP ID 4213825, SNP ID 3488617, SNP ID 3610210, SNP ID 3451239, SNP ID 1582533, SNP ID 3488150, SNP ID 2770052, SNP ID 4141351, SNP ID 1335030, SNP ID 2211665, and SNP ID 4538418.  
   
   
       23 . The method of  claim 21 , wherein the effect is selected from: 
 (a) increased or decreased expression of the gene or gene product in the presence of the modulator;    (b) increased or decreased activity of the gene product in the presence of the modulator; and,    (c) an altered expression pattern of the gene or gene product in the presence of the modulator.    
   
   
       24 . A kit for treatment of a breast cancer phenotype, the kit comprising a modulator identified by the method of  claim 21  and instructions for administering the modulator to a patient to treat the phenotype.  
   
   
       25 . A system for identifying a breast cancer phenotype for an organism or biological sample derived therefrom, the system comprising: 
 a) a set of marker probes or primers configured to detect at least one allele of one or more polymorphism or linked locus, wherein the polymorphism is selected from SNP ID 2312116, SNP ID 1622530, SNP ID 3712013, SNP ID 1509710, SNP ID 843029, SNP ID 1990126, SNP ID 604819, SNP ID 3025734, SNP ID 1152499, SNP ID 4415909, SNP ID 1732681, SNP ID 4281579, SNP ID 4454457, SNP ID 2616199, SNP ID 1720694, SNP ID 4077723, SNP ID 3711990, SNP ID 3337858, SNP ID 4093095, SNP ID 4213825, SNP ID 3488617, SNP ID 3610210, SNP ID 3451239, SNP ID 1582533, SNP ID 3488150, SNP ID 2770052, SNP ID 4141351, SNP ID 1335030, SNP ID 2211665, and SNP ID 4538418;    b) a detector that is configured to detect one or more signal outputs from the set of marker probes or primers, or an amplicon produced from the set of marker probes or primers, thereby identifying the presence or absence of the allele; and,    c) system instructions that correlate the presence or absence of the allele with a predicted phenotype.    
   
   
       26 . The system of  claim 25 , wherein the set of marker probes or primers detects a polymorphism in a gene selected from the group consisting of: FGFR2, A2BP1, TNRC9, H19, FSTL5, LSP1, LOC388927, UNQ9391, HCN1, LOC441192, TNRC9, NR3C2, KIAA0826, FLJ31033, AACS, FRMD4A and SEC31L2.  
   
   
       27 . The system of  claim 25 , wherein the set of marker probes or primers detects a plurality of polymorphisms in a plurality of said genes or genetic loci.  
   
   
       28 . The system of  claim 25 , wherein the set of marker probes or primers detects at least one polymorphism in each of: FGFR2, A2BP1, TNRC9, H19, and FSTL5.  
   
   
       29 . The system of  claim 25 , wherein the set of marker probes or primers detects at least one polymorphism selected from a polymorphism of: SNP ID 2312116, SNP ID 1622530, SNP ID 3712013, SNP ID 1509710, and SNP ID 843029.  
   
   
       30 . The system of  claim 25 , wherein the detector detects one or more light emission, wherein the light emission is indicative of the presence or absence of the allele.  
   
   
       31 . The system of  claim 25 , wherein the instructions comprise at least one look-up table that includes a correlation between the presence or absence of the allele and the phenotype.  
   
   
       32 . The system of  claim 25 , wherein the system comprises a sample.  
   
   
       33 . The system of  claim 32 , wherein the sample comprises genomic DNA, amplified genomic DNA, cDNA, amplified cDNA, RNA, or amplified RNA.  
   
   
       34 . The system of  claim 32 , wherein the sample is derived from a mammal.