Composition for detecting the response of rectal adenocarcinomas to radiochemotherapy

Abstract

A cDNA array (9984 genes) was used for expression profiling in rectal adenocarcinoma. The expression data were correlated to responsiveness to chemotherapy followed by radiotherapy. A set of 54 genes was found that were differentially expressed in responders vs. non-responders. The genes may be used as prognostic markers for determining whether a rectal adenocarcinoma is responsive to radiohemotherapy.

1 - 81 . (canceled) 
     
     
         82 . A composition comprising at least 5 isolated nucleic acids, each of which hybridizes specifically under conditions of high stringency to part or all of a coding sequence whose expression is correlated with responsiveness of a rectal adenocarcinoma to radiochemotherapy. 
     
     
         83 . The composition of  claim 82 , which comprises at least 5 isolated nucleic acids of at least about 15 contiguous nucleotides selected from nucleic acids that correspond to genes 1-54 from Table 3, and comprises no more than 9,000 total isolated nucleic acids. 
     
     
         84 . The composition of  claim 83 , wherein the nucleic acids that correspond to genes 1-54 of Table 3 are selected from:
 (a) nucleic acids that comprise the sequences of SEQ ID NOs: 1-58 or 113-123;   (b) nucleic acids that comprise sequences that are at least about 90% identical to the sequences of SEQ ID NOs: 1-58 or 113-123;   (c) nucleic acids that comprise sequences encoding polypeptides represented by SEQ ID NOs: 59-112;   (d) nucleic acids that comprise sequences of active fragments of the nucleic acids of (a), (b), or (c);   (e) nucleic acids that comprise sequences of active variants of the nucleic acids of (a), (b), or   (c) and/or   (f) nucleic acids that comprise complete complements of the sequences of any of the nucleic acids (a)-(e);   
       wherein the nucleic acids hybridize specifically under conditions of high stringency to nucleic acids represented by SEQ ID NOs: 1-58 or 113-123, or to complements thereof. 
     
     
         85 . The composition of  claim 83 , wherein the at least 5 isolated nucleic acids correspond to genes 1-12 or 42-44 of Table 3. 
     
     
         86 . The composition of  claim 85 , wherein the nucleic acids corresponding to genes 1-12 or 42-44 of Table 3 are selected from:
 (a) nucleic acids that comprise sequences comprising SEQ ID NOs: 1-15, 113-114, 46-48, or 120;   (b) nucleic acids that comprise sequences that are at least about 90% identical to SEQ ID NOs: 1-15, 113-114, 46-48, or 120;   (c) nucleic acids that comprise sequences encoding polypeptides represented by SEQ ID NOs 59-72 or 102-104;   (d) nucleic acids that comprise sequences of active fragments of the nucleic acids of (a), (b), or (c);   (e) nucleic acids that comprise sequences of active variants of the nucleic acids of (a), (b), or (c); and/or   (f) nucleic acids that comprise complete complements of the sequences of any of the nucleic acids (a)-(e);   
       wherein the nucleic acids hybridize specifically under conditions of high stringency to nucleic acids represented by SEQ ID NOs: 1-15, 113-114, 46-48 and 120, or to complements thereof. 
     
     
         87 . A composition comprising at least 5 isolated, antigenic, polypeptides for use in generating antibodies for detecting the response of a rectal adenocarcinoma to radiochemotherapy, wherein the polypeptides are polypeptides whose expression is correlated with responsiveness of the adenocarcinoma to radiochemotherapy. 
     
     
         88 . The composition of  claim 87 , wherein the at least 5 isolated, antigenic, polypeptides are selected from polypeptides that correspond to genes 1-54 from Table 3. 
     
     
         89 . The composition of  claim 88 , wherein the composition comprises polypeptides selected from:
 (a) polypeptides comprising SEQ ID NOs: 59-112;   (b) polypeptides encoded by polynucleotides comprising SEQ ID NOs: 1-58 or 113-123;   (c) polypeptides whose sequences are at least about 90% identical to SEQ ID NOs: 59-112;   (d) active variants of (a), (b) or (c); and/or   (e) antigenic fragments of (a), (b) or (c).   
     
     
         90 . The composition of  claim 88 , wherein the polypeptides are selected from polypeptides corresponding to genes 1- 12 or 42-44 from Table 3. 
     
     
         91 . The composition of  claim 90 , wherein the composition comprises polypeptides selected from:
 (a) polypeptides comprising SEQ ID NOs: 59-72 or 102-104;   (b) polypeptides encoded by polynucleotides comprising SEQ ID NOs: 1-15, 113-114, 46-48 or 120;   (c) polypeptides that are at least about 90% identical to SEQ ID NOs: 59-72 or 102-104;   (d) active variants of (a), (b), or (c); and/or   (e) antigenic fragments of (a), (b), or (c).   
     
     
         92 . A composition comprising at least 5 isolated antibodies, selected from antibodies that are specific for polypeptides corresponding to genes 1-54 of Table 3. 
     
     
         93 . The composition of  claim 92 , wherein the antibodies are specific for polypeptides selected from:
 (a) polypeptides comprising SEQ ID NOs: 59-112;   (b) polypeptides encoded by polynucleotides comprising SEQ ID NOs: 1-58 or 113-123;   (c) polypeptides whose sequences are at least about 90% identical to SEQ ID NOs: 59-112;   (d) active variants of (a), (b) or (c); and/or   (e) antigenic fragments of (a), (b) or (c).   
     
     
         94 . The composition of  claim 92 , wherein the antibodies are specific for polypeptides selected from polypeptides corresponding to genes 1- 12 or 42-44 from Table 3. 
     
     
         95 . The composition of  claim 94 , wherein the antibodies are specific for polypeptides selected from:
 (a) polypeptides comprising SEQ ID NOs: 59-72 or 102-104;   (b) polypeptides encoded by polynucleotides comprising SEQ ID NOs: 1-15, 113-114, 46-48 or 120;   (c) polypeptides that are at least about 90% identical to SEQ ID NOs: 59-72 or 102-104;   (d) active variants of (a), (b), or (c); and/or   (e) antigenic fragments of (a), (b), or (c).