Proteomics analysis and discovery through dna and rna sequencing, systems and methods

Abstract

Specific mutations of FGFR3 (S249C) and of TP53 (V272M) are identified as being characteristic of breast cancer, and of having utility in diagnosis and prognosis of an individual with breast cancer. Systems and methods useful for identification of such mutations are also presented.

What is claimed is: 
     
         1 . A method of identifying an individual having susceptibility to breast cancer, comprising:
 obtaining a first tissue sample from the individual;   performing a first genomic analysis on the tissue sample; and   identifying a first mutation at a position in an FGFR3 gene corresponding to amino acid 249 and identifying a second mutation at a position in a TP53 gene corresponding to amino acid 272.   
     
     
         2 . The method of  claim 1 , wherein the first genomic analysis is performed without reference to a second genomic analysis performed on a second tissue sample from the individual. 
     
     
         3 . The method of  claim 1 , wherein the first genomic analysis is sequencing of a cDNA prepared from an mRNA obtained from the first sample, wherein the cDNA does not include an intron present in the corresponding genomic DNA of the first sample. 
     
     
         4 . The method of  claim 1 , wherein the first mutation is an S249C mutation. 
     
     
         5 . The method of  claim 1  or  claim 5 , wherein the second mutation is a V272M mutation. 
     
     
         6 . A method of identifying a tissue sample as having originated from a breast cancer, comprising:
 obtaining a tissue sample;   performing a genomic analysis on the tissue sample; and   identifying a first mutation at a position in an FGFR3 gene corresponding to amino 249 and identifying a second mutation in a TP53 gene at a position corresponding to amino acid 272.   
     
     
         7 . The method of  claim 6 , wherein the genomic analysis is performed without reference to a second genomic analysis performed on a second tissue sample from the same subject. 
     
     
         8 . The method of  claim 6 , wherein the genomic analysis is sequencing of a cDNA prepared from an mRNA obtained from the first sample, wherein the cDNA does not include an intron present in the corresponding genomic DNA of the first sample. 
     
     
         9 . The method of  claim 6 , wherein the first mutation is an S249C mutation. 
     
     
         10 . The method of  claim 6  or  claim 9 , wherein the second mutation is a V272M mutation. 
     
     
         11 . A method of identifying a plurality of tumor markers, comprising:
 obtaining a first sample from the neoplasm;   performing a first genomic analysis on the tissue sample to obtain a sequence data;   comparing the sequence data to a mutation catalog to identify a plurality of mutations, wherein the mutation catalog comprises frequencies of the association of genetic variations with neoplasms; and, a subset of the plurality of mutations as tumor markers when each member of the subset is identified by comparison to the mutation catalog as having a frequency greater than 0.6%.   
     
     
         12 . The method of  claim 11 , wherein comparing the sequence data is performed without reference to a tissue sample obtained from a non-neoplasm source. 
     
     
         13 . The method of  claim 11 , wherein the first genomic analysis is sequencing of a cDNA prepared from an mRNA obtained from the sample, wherein the cDNA does not include an intron present in the corresponding genomic DNA of the sample. 
     
     
         14 . The method of  claim 11 , wherein the plurality of mutations comprises a first tumor marker and a second tumor marker. 
     
     
         15 . The method of  claim 14 , wherein the neoplasm is a breast cancer. 
     
     
         16 . The method of  claim 15 , wherein the first tumor marker is a mutation of TP53 at a position corresponding to amino acid 272 and the second tumor marker is a mutation of FGFR3 at a position corresponding to amino acid 249.