US2003175768A1PendingUtilityA1

Method for early diagnosis of, and determination of prognosis in, cancer

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Assignee: UNIV CALIFORNIAPriority: Jun 23, 1998Filed: Dec 20, 2002Published: Sep 18, 2003
Est. expiryJun 23, 2018(expired)· nominal 20-yr term from priority
Inventors:Dennis A. CarsonMathias SchmidCarlos J. Carrera
C12Q 1/6886C12Q 2600/112
56
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Claims

Abstract

The invention provides a method for diagnosis of, and determining a prognosis for, cancer causatively associated with derangements of chromosome 9p21. Underlying the invention is the discovery that such derangements have their genesis in deletions occurring centromeric to STS 3.21, most often including breakpoints in exon 8 and/or between exons 4 and 5 of the gene which codes for methylthioadenosine phosphorylase. As the cancer and tumor development advance, deletions in 9p21 progress centromerically from the genesis point toward the gene encoding p16. Thus, the method of the invention is performed by determining whether (a) portions of the 9p21 region including and telomeric to STS 3.21 are deleted; and (b) portions of the 9p21 region centromeric to STS 3.21 are deleted; wherein a positive finding in step (a) and a negative finding in step (b) are indicative of a cancer in an early stage of tumor development and a positive finding in step (b) is indicative of a cancer in an advanced stage of tumor development.

Claims

exact text as granted — not AI-modified
The invention claimed is:  
     
         1 . A method for diagnosis of, and determining a prognosis for, cancer causatively associated with derangement of chromosome 9p21, the method comprising: 
 (a) determining whether any portion of the 9p21 chromosome including and telomeric to STS 3.21 is deleted; and,    (b) determining whether any portion of the 9p21 chromosome centromeric to STS 3.21 is deleted;    wherein a positive finding in step (a) and a negative finding in step (b) are indicative of a cancer at an early stage of tumor development; and,    wherein further a positive finding in step (b) is indicative of a cancer at an advanced stage of tumor development.    
     
     
         2 . A method for diagnosis of, and determing a prognosis for, cancer causatively associated with derangements of chromosome 9p21, the method comprising: 
 (a) determining whether any portion of the gene encoding MTAP is deleted; and,    (b) determining whether any portion of the 9p21 chromosome centomeric to STS 3.21 is deleted;    wherein a positive finding in step (a) and a negative finding in step (b) are indicative of a cancer at an early stage of tumor development; and,    wherein further a positive finding in step (b) is indicative of a cancer at an advanced stage of tumor development.    
     
     
         3 . The method according to  claim 2  wherein step (a) comprises determining whether exon  8  of the gene coding for MTAP is deleted.  
     
     
         4 . The method according to  claim 2  wherein step (a) comprises determining whether the region from exon  4  to exon  5  of the gene coding for MTAP is deleted.  
     
     
         5 . The method according to  claim 2  wherein step (b) comprises determining whether any portion of the gene coding for p16 is deleted.  
     
     
         6 . A method for diagnosis of, and determining a prognosis for, cancer causatively associated with derangements of chromosome 9p21, the method comprising: 
 (a) determining whether any portion of the gene encoding MTAP is deleted; and,    (b) determining whether any portion of the gene coding for p16 is deleted;    wherein a positive finding in step (a) and a negative finding in step (b) are indicative of a cancer at an early stage of tumor development; and, wherein further a positive finding in step (a) and a positive finding in step (b) is highly indicative of a cancer at an advanced stage of tumor development.    
     
     
         7 . The method according to  claim 1 , further comprising the use in step (a) of primer pairs selected from the group of nucleotides consisting of SEQ.ID.No.: 3 and 4; SEQ.ID.No.: 21 and 22, and SEQ.ID.No.: 23 and 24.  
     
     
         8 . The method according to  claim 2 , further comprising the use in step (a) of primer pairs selected from the group of nucleotides consisting of SEQ.ID.No.: 3 and 4; SEQ.ID.No.: 21 and 22, and SEQ.ID.No.: 23 and 24.  
     
     
         9 . The method according to  claim 6 , further comprising the use in step (a) of primer pairs selected from the group of nucleotides consisting of SEQ.ID.No.: 3 and 4; SEQ.ID.No.: 21 and 22, and SEQ.ID.No.: 23 and 24.  
     
     
         10 . The method according to  claim 1 , further comprising the use in step (b) of primer pairs selected from the group of nucleotides consisting of SEQ.ID.No.: 5 and 6; SEQ.ID.No.: 7 and 8; SEQ.ID.No.: 9 and 10; SEQ.ID.No.: 11 and 12; SEQ.ID.No.: 13 and 14; SEQ.ID.No.: 15 and 16; and, SEQ.ID.No.: 17 and 18.  
     
     
         11 . The method according to  claim 2 , further comprising the use in step (b) of primer pairs selected from the group of nucleotides consisting of SEQ.ID.No.: 5 and 6; SEQ.ID.No.: 7 and 8; SEQ.ID.No.: 9 and 10; SEQ.ID.No.: 11 and 12; SEQ.ID.No.: 13 and 14 SEQ.ID.No.: 15 and 16; and, SEQ.ID.No.: 17 and 18.  
     
     
         12 . The method according to  claim 6 , further comprising the use in step (b) of primer pairs selected from the group of nucleotides consisting of SEQ.ID.No.: 5 and 6; SEQ.ID.No.: 7 and 8; SEQ.ID.No.: 9 and 10; SEQ.ID.No.: 11 and 12; SEQ.ID.No.: 13 and 14; SEQ.ID.No.: 15 and 16; and, SEQ.ID.No.: 17 and 18.  
     
     
         13 . The method according to  claim 1 , further comprising the use of the primer pair of SEQ.ID.No.: 1 and 2 as a control for step (a).  
     
     
         14 . The method according to  claim 2 , further comprising the use of the primer pair of SEQ.ID.No.: 1 and 2 as a control for step (a).  
     
     
         15 . The method according to  claim 6 , further comprising the use of the primer pair of SEQ.ID.No.: 1 and 2 as a control for step (a).  
     
     
         16 . The method according to  claim 1 , wherein the cancer is a glioma.  
     
     
         17 . The method according to  claim 2 , wherein the cancer is a glioma.  
     
     
         18 . The method according to  claim 6 , wherein the cancer is a glioma.  
     
     
         19 . The method according to  claim 1 , wherein the cancer is a primary lymphoid malignancy.  
     
     
         20 . The method according to  claim 2 , wherein the cancer is a primary lymphoid malignancy.  
     
     
         21 . The method according to  claim 6 , wherein the cancer is a primary lymphoid malignancy.  
     
     
         22 . The method according to  claim 1 , wherein the cancer is non-small cell lung cancer.  
     
     
         23 . The method according to  claim 2 , wherein the cancer is non-small cell lung cancer.  
     
     
         24 . The method according to  claim 6 , wherein the cancer is non-small cell lung cancer.  
     
     
         25 . The method according to  claim 1 , wherein the cancer is a melanoma.  
     
     
         26 . The method according to  claim 2 , wherein the cancer is a melanoma.  
     
     
         27 . The method according to  claim 6 , wherein the cancer is a melanoma.  
     
     
         28 . A kit for use in the method of  claim 1 , the kit comprising: primers for use in step (a) of the method; primers for use in step (b) of the method; at least one set of primers for use as a control; and, a staging reference.  
     
     
         29 . A kit for use in the method of  claim 2 , the kit comprising: primers for use in step (a) of the method; primers for use in step (b) of the method; at least one set of primers for use as a control; and, a staging reference.  
     
     
         30 . A kit for use in the method of  claim 6 , the kit comprising: primers for use in step (a) of the method; primers for use in step (b) of the method; at least one set of primers for use as a control; and, a staging reference.  
     
     
         31 . The kit according to  claim 28 , wherein the primers for use in step (a) are selected from the group of nucleotides consisting of SEQ.ID.No.: 3 and 4; SEQ.ID.No.: 21 and 22, and SEQ.ID.No.: 23 and 24.  
     
     
         32 . The kit according to  claim 29 , wherein the primers for use in step (a) are selected from the group of nucleotides consisting of SEQ.ID.No.: 3 and 4; SEQ.ID.No.: 21 and 22, and SEQ.ID.No.: 23 and 24.  
     
     
         33 . The kit according to  claim 30 , wherein the primers for use in step (a) are selected from the group of nucleotides consisting of SEQ.ID.No.: 3 and 4; SEQ.ID.No.: 21 and 22, and SEQ.ID.No.: 23 and 24.  
     
     
         34 . The kit according to  claim 28 , wherein the primers for use in step (b) are selected from the group of nucleotides consisting of SEQ.ID.No.: 5 and 6; SEQ.ID.No.: 7 and 8; SEQ.ID.No.: 9 and 10; SEQ.ID.No.: 11 and 12; SEQ.ID.No.: 13 and 14; SEQ.ID.No.: 15 and 16; and, SEQ.ID.No.: 17 and 18.  
     
     
         35 . The kit according to  claim 29  wherein the primers for use in step (b) are selected from the group of nucleotides consisting of SEQ.ID.No.: 5 and 6; SEQ.ID.No.: 7 and 8; SEQ.ID.No.: 9 and 10; SEQ.ID.No.: 11 and 12; SEQ.ID.No.: 13 and 14; SEQ.ID.No.: 15 and 16; and, SEQ.ID.No.: 17 and 18.  
     
     
         36 . The kit according to  claim 30 , wherein the primers for use in step (b) are selected from the group of nucleotides consisting of SEQ.ID.No.: 5 and 6; SEQ.ID.No.: 7 and 8; SEQ.ID.No.: 9 and 10; SEQ.ID.No.: 11 and 12; SEQ.ID.No.: 13 and 14; SEQ.ID.No.: 15 and 16; and, SEQ.ID.No.: 17 and 18.  
     
     
         37 . The kit according to  claim 28 , wherein the primer for use as a control consist of SEQ.ID.No.: 1 and 2 as a control for step (a).  
     
     
         38 . The kit according to  claim 29 , wherein the primer for use as a control consist of SEQ.ID.No.: 1 and 2 as a control for step (a).  
     
     
         39 . The kit according to  claim 30 , wherein the primer for use as a control consist of SEQ.ID.No.: 1 and 2 as a control for step (a).  
     
     
         40 . The kit according to  claim 28 , wherein the staging reference comprises the data set forth in FIG. 1.  
     
     
         41 . The kit according to  claim 29 , wherein the staging reference comprises the data set forth in FIG. 1.  
     
     
         42 . The kit according to  claim 30 , wherein the staging reference comprises the data set forth in FIG. 1.

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