Tert promoter mutations in cancer

Abstract

The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions related to certain promoter mutations in cancer. In one embodiment, a method for treating a subject having thyroid cancer comprises the steps of (a) obtaining a biological sample from the subject; (b) performing an assay on the sample obtained from the subject to identify a mutation at 1 295 228 C>T (C228T) and 1 295 250 C>T (C250T), corresponding to −124 C>T and −146 C>T from the translation start site in the promoter of the telomerase reverse transcriptase (TERT) gene; (c) identifying the subject as having or likely to develop aggressive thyroid cancer if the C228T and/or C250T mutation is identified; and (d) treating the subject with one or more treatment modalities appropriate for a subject having or likely to develop aggressive thyroid cancer.

We claim: 
     
         1 . A method for treating a subject having thyroid cancer comprising the steps of:
 a. obtaining a biological sample from the subject;   b. performing an assay on the sample obtained from the subject to identify a mutation at 1 295 228 C>T (C228T) and 1 295 250 C>T (C250T), corresponding to −124 C>T and −146 C>T from the translation start site in the promoter of the telomerase reverse transcriptase (TERT) gene;   c. identifying the subject as having or likely to develop aggressive thyroid cancer if the C228T and/or C250T mutation is identified; and   d. treating the subject with one or more treatment modalities appropriate for a subject having or likely to develop aggressive thyroid cancer.   
     
     
         2 . The method of  claim 1 , wherein the assay of step (b) comprises sequencing of the TERT promoter region comprising −124 and −146 from the translation start site in the promoter of TERT. 
     
     
         3 . The method of  claim 1 , wherein the assay of step (b) comprises the steps of:
 i. extracting DNA from the biological sample;   ii. contacting the DNA with a primer that specifically hybridizes to the TERT gene;   iii. amplifying by polymerase chain reaction (PCR) a region of the TERT gene that comprises −124 and −146 from the translation start site in the promoter of TERT; and   iv. sequencing the amplification product to identify the presence of the C228T and/or C250T mutation.   
     
     
         4 . The method of  claim 1 , wherein the treatment modality for aggressive thyroid cancer comprises thyroidectomy, hemithyroidectomy, radioactive iodine therapy, and combinations thereof 
     
     
         5 . The method of  claim 1 , wherein the treatment modality comprises administering to the subject a TERT inhibitor. 
     
     
         6 . A method for identifying a subject as having or likely to develop aggressive thyroid cancer comprising the steps of:
 a. obtaining a biological sample from the subject;   b. performing an assay on the sample obtained from the subject to identify a mutation at 1 295 228 C>T (C228T) and 1 295 250 C>T (C250T), corresponding to −124 C>T and −146 C>T from the translation start site in the promoter of the telomerase reverse transcriptase (TERT) gene;   c. identifying the subject as having or likely to develop aggressive thyroid cancer if the C228T and/or C250T mutation is identified.   
     
     
         7 . The method of  claim 6 , wherein the assay of step (b) comprises sequencing of the TERT promoter region comprising −124 and −146 from the translation start site in the promoter of TERT. 
     
     
         8 . The method of  claim 6 , wherein the assay of step (b) comprises the steps of:
 i. extracting DNA from the biological sample;   ii. contacting the DNA with a primer that specifically hybridizes to the TERT gene;   iii. amplifying by polymerase chain reaction (PCR) a region of the TERT gene that comprises −124 and −146 from the translation start site in the promoter of TERT; and   iv. sequencing the amplification product to identify the presence of the C228T and/or C250T mutation.   
     
     
         9 . The method of  claim 6 , further comprising the step of administering a treatment modality appropriate for a subject having or likely to develop aggressive thyroid cancer. 
     
     
         10 . The method of  claim 9 , wherein the treatment modality for aggressive thyroid cancer comprises thyroidectomy, hemithyroidectomy, radioactive iodine therapy, and combinations thereof. 
     
     
         11 . The method of  claim 9 , wherein the treatment modality comprises administering to the subject a TERT inhibitor.