Breast cancer splice variants

Abstract

Provided herein, in some embodiments, are methods, compositions, and systems for identifying alternatively spliced tumor-specific exon inclusion and exclusion events that can be used for survival prognosis.

1 . A method comprising assaying nucleic acids of a sample for the presence or absence of:
 a target exon comprising a nucleotide sequence of any one of SEQ ID NOS: 22-24, 26-36, 38-40, 73-75, 77-79, 82-100, 102-104;   (b) at least 2 target exons, wherein each target exon comprises a nucleotide sequence of any one of SEQ ID NOS: 23, 27, 35, 85, 88, 89, 98, 101, 102, or 104;   (c) at least 3 target exons, wherein each target exon comprises a nucleotide sequence of any one of SEQ ID NOS: 21, 23, 27, 30, 31, 32, 35, 36, 39, 85, 87-89, 91, 94, 98, or 101-104; or   (d) at least 8 different target exons, wherein each target exon comprises a nucleotide sequence of any one of SEQ ID NOs: 21-40 or 73-104.   
     
     
         2 . The method of  claim 1 , wherein the target exon comprises a nucleotide sequence of any one of SEQ ID NOS: 27, 98, 102, or 104. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein each target exon comprises a nucleotide sequence of any one of SEQ ID NOS: 27, 98, 101, 102, or 104. 
     
     
         5 .- 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the sample is a breast tissue sample. 
     
     
         8 . The method of  claim 7 , wherein the sample is obtained from a subject suspect of having, at risk of, or diagnosed with breast cancer. 
     
     
         9 . The method of  claim 8 , wherein the subject is a female subject. 
     
     
         10 . The method of  claim 1  any one of  claim 1 , wherein the nucleic acids comprise messenger ribonucleic acid (mRNA). 
     
     
         11 . The method of  claim 1 , wherein the nucleic acids comprise complementary deoxyribonucleic acid (cDNA) synthesized from mRNA obtained from the sample. 
     
     
         12 . The method of  claim 1 , further comprising detecting the presence of a target exon comprising a nucleotide sequence of any one of SEQ ID NOs: 24, 28, 31, 33, and/or 38 or the absence of a target exon comprising a nucleotide sequence of any one of SEQ ID NOs: 82, 87 and/or 91, and assigning a favorable survival prognosis to the sample. 
     
     
         13 . The method of  claim 1 , further comprising detecting the presence of a target exon comprising a nucleotide sequence of any one of SEQ ID NOs: 21-23, 25-27, 29, 30, 32, and/or 34-40 or the absence of a target exon comprising a nucleotide sequence of any one of SEQ ID NOs: 73-81, 83-86, 88-90, and/or 92-104, and assigning an unfavorable survival prognosis to the sample. 
     
     
         14 . A complementary deoxyribonucleic acid (cDNA) comprising a nucleotide sequence of any one of SEQ ID NOs: 1-20 or 105-136. 
     
     
         15 . The cDNA of  claim 14  comprising a nucleotide sequence of any one of SEQ ID NOs: 22-24, 27-34, 36, 38, or 40. 
     
     
         16 . A composition comprising the cDNA of  claim 14 . 
     
     
         17 . The composition of  claim 16  further comprising a probe that binds the cDNA or a pair of primers that bind the cDNA. 
     
     
         18 . (canceled) 
     
     
         19 . A composition comprising (a) a messenger ribonucleic acid (mRNA) comprising a nucleotide sequence of any one of SEQ ID NOs: 1-20 or 105-136 and (b) a probe that binds a nucleotide sequence of any one of SEQ ID NOs: 1-20 or 105-136 or a pair of primers that bind a nucleotide sequence of any one of SEQ ID NOs: 1-20 or 105-136. 
     
     
         20 . The composition of  claim 17 , wherein the probe comprises a detectable label or the primers comprise a detectable label. 
     
     
         21 . (canceled) 
     
     
         22 . The composition of  claim 19 , wherein the probe comprises a detectable label or the primers comprise a detectable label. 
     
     
         23 . A kit comprising:
 a molecule that can detect the presence or absence of a target exon comprising a nucleotide sequence of any one of SEQ ID NOS: 22-24, 26-36, 38-40, 73-75, 77-79, 82-100, 102-104, and a detection reagent selected from buffers, salts, polymerases, and deoxyribonucleotide triphosphates (dNTPs),   molecules that can detect the presence or absence of at least 2 target exons, wherein each of the at least 2 target exons comprises a nucleotide sequence of any one of SEQ ID NOs: 23, 27, 35, 85, 88, 89, 98, 101, 102, or 104, and a detection reagent selected from buffers, salts, polymerases, and dNTPs,   molecules that can detect the presence or absence of at least 3 target exons, wherein each of the at least 3 target exons comprises a nucleotide sequence of any one of SEQ ID NOS: 21, 23, 27, 30, 31, 32, 35, 36, 39, 85, 87-89, 91, 94, 98, or 101-104, and a detection reagent selected from buffers, salts, polymerases, and dNTPs, or   molecules that can detect the presence or absence of at least 8 different target exons, wherein each of the at least 8 target exons comprises a nucleotide sequence of any one of SEQ ID NOs: 21-40 or 73-104, and a detection reagent selected from buffers, salts, polymerases, and dNTPs.   
     
     
         24 . The kit of  claim 23 , wherein the molecule comprise a probe or primer that bind a nucleic acid comprising a nucleotide sequence of any one of SEQ ID NOS: 22-24, 26-36, 38-40, 73-75, 77-79, 82-100, 102-104. 
     
     
         25 - 27 . (canceled) 
     
     
         28 . The kit of  claim 24 , wherein the probe or primer comprises a detectable label.