Methods And Compositions For Detection Of Cowden Syndrome (CS) and CS-Like Syndrome

Abstract

The invention is directed to methods of detecting Cowden syndrome (CS) or CS-like syndrome in an individual or determining whether an individual is at risk for developing Cowden syndrome (CS) or CS-like syndrome comprising detecting the presence of a mutated succinate dehydrogenase B (SDHB), mutated succinate dehydrogenase D (SDHD) or combination thereof in the individual, wherein detection of a mutated SDHB, SDHD or a combination thereof indicates that the individual is positive for, or at risk of developing, CS or CS-like syndrome. The invention is also directed to an article of manufacture for detecting Cowden syndrome (CS) or Cowden-like syndrome in an individual, comprising one or more agents that detects mutated succinate dehydrogenase B (SDHB), mutated succinate dehydrogenase D (SDHD) or combination thereof in the individual, and instructions for use.

1 . A method of detecting Cowden syndrome (CS) or CS-like syndrome in an individual comprising detecting the presence of a mutated succinate dehydrogenase B (SDHB), mutated succinate dehydrogenase D (SDHD) or combination thereof in the individual, wherein detection of a mutated SDHB, SDHD or a combination thereof indicates that the individual is positive for CS or CS-like syndrome. 
     
     
         2 . The method of  claim 1  wherein the mutated SDHB is an Ala3Gly mutation, a Ser163Pro mutation or a combination thereof. 
     
     
         3 . The method of  claim 1  wherein the mutated SDHD is a Gly12Ser mutation, a His 50Arg mutation, a His145Asn mutation or a combination thereof. 
     
     
         4 . The method of  claim 1  wherein the individual is negative for a mutated phosphatase and tensin homolog deleted on chromsome ten (PTEN). 
     
     
         5 . The method of  claim 4  wherein the individual has elevated expression levels of maganese superoxide dismutase. 
     
     
         6 . The method of  claim 1  wherein the individual has a carcinoma of the breast, thyroid, kidney or a combination thereof. 
     
     
         7 - 8 . (canceled) 
     
     
         9 . The method of  claim 1  wherein the presence of a mutated succinate dehydrogenase B (SDHB), mutated succinate dehydrogenase D (SDHD) or combination thereof is detected in the individual by determining:
 the sequence of the SDHB, SDHD or combination thereof, 
 the function of the SDHB, SDHD or combination thereof, 
 or the sequence and the function. 
 
     
     
         10 - 17 . (canceled) 
     
     
         18 . The method of  claim 1  further comprising obtaining a sample from the individual. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 1  wherein the individual is a human. 
     
     
         21 . A method of determining whether an individual is at risk for developing Cowden syndrome (CS) or CS-like syndrome comprising detecting the presence of a mutated succinate dehydrogenase B (SDHB), mutated succinate dehydrogenase D (SDHD) or combination thereof in the individual, wherein detection of a mutated SDHB, SDHD or a combination thereof indicates that the individual is at risk for developing for CS or CS-like syndrome. 
     
     
         22 . The method of  claim 21  wherein the mutated SDHB is an Ala3Gly mutation, a Ser163Pro mutation or a combination thereof. 
     
     
         23 . The method of  claim 21  wherein the mutated SDHD is a Gly12Ser mutation, a His50Arg mutation, a His145Asn mutation or a combination thereof. 
     
     
         24 . The method of  claim 21  wherein the individual is negative for a mutated phosphatase and tensin homolog deleted on chromsome ten (PTEN). 
     
     
         25 . The method of  claim 24  wherein the individual has elevated expression levels of maganese superoxide dismutase. 
     
     
         26 . The method of  claim 21  wherein the individual has a carcinoma of the breast, thyroid, kidney or a combination thereof. 
     
     
         27 - 28 . (canceled) 
     
     
         29 . The method of  claim 21  wherein the presence of a mutated succinate dehydrogenase B (SDHB), mutated succinate dehydrogenase D (SDHD) or combination thereof is detected in the individual by determining
 the sequence of the SDHB, SDHD or combination thereof, 
 the function of the SDHB, SDHD or combination thereof, 
 or both the sequence and the function. 
 
     
     
         30 - 37 . (canceled) 
     
     
         38 . The method of  claim 21  further comprising obtaining a sample from the individual. 
     
     
         39 . (canceled) 
     
     
         40 . The method of  claim 21  wherein the individual is a human. 
     
     
         41 . An article of manufacture for detecting Cowden syndrome (CS) or Cowden-like syndrome in an individual, comprising one or more agents that detects mutated succinate dehydrogenase B (SDHB), mutated succinate dehydrogenase D (SDHD) or combination thereof in the individual, and instructions for use. 
     
     
         42 . The article of manufacture of  claim 41  wherein the mutated SDHB is an Ala3Gly mutation, a Ser163Pro mutation or a combination thereof. 
     
     
         43 . The article of manufacture of  claim 41  wherein the mutated SDHD is a Gly12Ser mutation, a His50Arg mutation, a His145Asn mutation or a combination thereof. 
     
     
         44 - 47 . (canceled)