Papanicolaou test for ovarian and endometrial cancers

Abstract

The recently developed liquid-based Papanicolaou (Pap) smear allows not only cytologic evaluation but also collection of DNA for detection of HPV, the causative agent of cervical cancer. We tested these samples to detect somatic mutations present in rare tumor cells that might accumulate in the cervix once shed from endometrial and ovarian cancers. A panel of commonly mutated genes in endometrial and ovarian cancers was assembled and used to identify mutations in all 46 endometrial or cervical cancer tissue samples. We were able also able to identify the same mutations in the DNA from liquid Pap smears in 100% of endometrial cancers (24 of 24) and in 41% of ovarian cancers (9 of 22). We developed a sequence-based method to query mutations in 12 genes in a single liquid Pap smear without prior knowledge of the tumor's genotype.

1 - 25 . (canceled) 
     
     
         26 . A method comprising:
 a) testing a liquid Pap specimen obtained from a human subject for at least one of the following nucleic acid mutations:
 i) FBXW7 1435C>T, 
 ii) PIK3CA 323G>A, 
 iii) TP53 328C>T, 
 iv) PIK3CA 263G>A, and 
 v) CTNNB1 100G>A; and 
   b) detecting the presence of at least one of the following:
 i) the T allele at position 1435 of FBXW7 gene; 
 ii) the A allele at position 323 of PIK3CA gene; 
 iii) the T allele at position 328 of TP53 gene; 
 iv) the A allele at position 263 of PIK3CA gene; and 
 v) the A allele at position 100 of CTNNB1 gene. 
   
     
     
         27 . The method of  claim 26 , wherein said human subject has an endometrial tumor. 
     
     
         28 . The method of  claim 26 , wherein said human subject has endometrial cancer. 
     
     
         29 . The method of  claim 26 , wherein the liquid Pap specimen is collected from the cervix. 
     
     
         30 . The method of  claim 26 , wherein the liquid Pap specimen comprises cells from the ectocervix. 
     
     
         31 . The method of  claim 26 , wherein the presence of the T allele at position 1435 of FBXW7 gene is detected. 
     
     
         32 . The method of  claim 26 , wherein the presence of the A allele at position 323 of PIK3CA gene is detected. 
     
     
         33 . The method of  claim 26 , wherein the presence of the T allele at position 328 of TP53 gene is detected. 
     
     
         34 . The method of  claim 26 , wherein the presence of the A allele at position 263 of PIK3CA gene is detected. 
     
     
         35 . The method of  claim 26 , wherein the presence of the A allele at position 100 of CTNNB1 gene is detected.