Diagnosis of cowden and cowden-like syndrome by detection of decreased killin expression

Abstract

A method of diagnosing Cowden syndrome (CS) and Cowden-like Syndrome (CLS) is described. The method includes diagnosing CS and CLS in a subject by identifying a decrease in expression of the KILLIN gene, or by identifying hypermethylation of the KILLIN promoter region. Kits for diagnosing CS and CLS by identifying subjects having KILLIN promoter region hypermethylation and primers specific for a methylated KILLIN promoter region are also described.

1 - 12 . (canceled) 
     
     
         13 . A kit for diagnosing Cowden Syndrome and Cowden-like Syndrome, comprising:
 a carrier compartmentalized to include a plurality of containers and to receive a DNA sample including the KILLIN promoter region from a subject therein;   the carrier comprising a first container including sodium bisulfate, and the solvents and reagents necessary to selectively convert unmethylated cytosine of the DNA sample into uracil;   a second container containing a PCR primer pair corresponding to the methylated base sequence of the KILLIN promoter region and the solvents and reagents necessary to obtain an amplified base sequence;   a third container containing a labeled probe complementary to the amplified base sequence; and   means for detecting the labeled probe to quantitatively analyze the amount of methylation of the KILLIN promoter region; and a KILLIN promoter region control.   
     
     
         14 . The kit of  claim 13 , wherein the kit further comprises instructions for use of the kit to compare the amount of methylation of the KILLIN promoter region in the DNA sample to a KILLIN promoter region control, wherein hypermethylation of the KILLIN promoter region indicates a diagnosis of Cowden syndrome or Cowden-like Syndrome for the subject. 
     
     
         15 . The kit of  claim 13 , wherein the PCR primer pair is SEQ ID NO: 12 and SEQ ID NO: 13. 
     
     
         16 . A pair of PCR primer sequences for DNA methylation analysis comprising a forward PCR primer and a reverse PCR primer, wherein the primers include from 20 to 25 nucleotides and are effective to amplify SEQ ID NO: 3 using the polymerase chain reaction. 
     
     
         17 . The PCR primer sequences of  claim 16 , wherein the forward PCR primer is SEQ ID NO: 12 and the reverse PCR primer is SEQ ID NO: 13. 
     
     
         18 . A method for treating a subject having Cowden syndrome or Cowden-like syndrome by administering to the subject a therapeutically effective amount of a DNA methyltransferase inhibitor. 
     
     
         19 . The method of  claim 18 , wherein the method further comprises administering a histone deacetylase inhibitor to the subject. 
     
     
         20 . The method of  claim 18 , wherein the subject has been found to lack germline PTEN mutation. 
     
     
         21 . The method of  claim 18 , wherein the subject is human.