APC gene and nucleic acid probes derived therefrom

Abstract

A human gene termed APC is disclosed. Methods and kits are provided for assessing mutations of the APC gene in hum tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as wel as in sporadic colorectal cancer patents. APC is expressed in most normal tissue. These results suggest that APC is a tumor suppressor.

We claim: 
     
       1. A cDNA molecule having the nucleotide sequence shown in SEQ ID NO: 1 or its complement. 
     
     
       2. An isolated DNA molecule having the nucleotide sequence shown in SEQ ID NO:1 or its complement. 
     
     
       3. A cDNA molecule which encodes a protein having the amino acid sequence shown in .[.FIG. 3 or 7 (.].SEQ ID NO: 7 or 2.[.).].. 
     
     
       4. An isolated DNA molecule which encodes a protein having the amino acid sequence shown in .[.FIG. 3 or 7 (.].SEQ ID NO: 7 or 2.[.).].. 
     
     
       5. A nucleic acid probe complementary to all or part of human wild-type APC gene coding sequences or the complement of said sequences such that said probe selectively hybridizes under stringent conditions to said APC gene or identifies endogenous, random modifications in said APC gene. 
     
     
       6. The nucleic acid probe of claim 5 which hybridizes to all or part of an exon selected from the group consisting of: (1) nucleotides 822 to 930; (2) nucleotides 931 to to 1309; (3) nucleotides 1406 to 1545; and (4) nucleotides 1956 to 2256 .Iadd.as shown in SEQ ID NO: 1.Iaddend.. 
     
     
       7. A set of probes useful for detecting alteration of wild-type APC genes comprising a plurality of nucleic acid probes wherein said set is complementary to all nucleotides of the APC gene coding sequences as shown in SEQ ID NO:1 or the complement of said sequences. 
     
     
       8. A pair of single stranded DNA primers for determination of a nucleotide sequence of an APC gene by polymerase chain reaction, the sequence of said primers being derived from said APC gene, wherein the use of said primers in a polymerase chain reaction results in synthesis of DNA having all or part of the sequence shown in .[.FIG. 7 (.].SEQ ID NO:1.[.).].. 
     
     
       9. The pair of primers of claim 8 which have restriction enzyme sites at each 5' end. 
     
     
       10. The pair of primers of claim 8 having sequences complementary to all or part of one or more APC introns.