b-catenin mutations are found in various human cancers. These mutations are very specific; they are in residues in the aminoterminal domain of the protein (see Figure). These residues can become phosphorylated and play a role in the destabilization of the protein. The mutations block phosphorylation and therefore lead to increased stability of the b-catenin protein. The table lists the frequency and the positions of point mutations. In some tumors, the entire amino-terminus is deleted.

updated Sept 1, 2000

Table kindly provided by Paul Polakis

Polakis P. Wnt signaling and cancer. Genes Dev. 2000 Aug 1;14(15):1837-51.

tissue freq. S29 Y30 L31 D32 S33 G34 I35 H36 S37 G38 A39 T40 T41 T42 A43 P44 S45 L46 S47 G48 K49 D reference comment
                                                  small>large
colorectal 9/202           1             3       5           samowitz both were MSI
colorectal 2/92                         1       1           kitaeva  
colorectal-w/o APC mutation 7/58                                             Iwao one at pos. fifty
colorectal-w/o APC mutation 13/27         2 1             3       5           sparks only 6/28 have APC mutations
colorectal HNPCC 12/28       2   2     1       2       5           miyaki  
colorectal w/ MSI 13/53                                 6           mirabelli-primdahl  
colorectal w/o MSI 0/27                                             mirabelli-primdahl  
desmoid, sporadic 1/1                         1                   shitoh  
desmoid, sporadic 22/42                         10       12           tejpar 9/42 APC w/ no overlap
endometrial w/ MSI 3/9       2 1                                   mirabelli-primdahl  
endometrial w/o MSI 10/20       3 1 2     3       1                   mirabelli-primdahl
gastric, Intestinal-type 7/26 2     5                                     park  
gastric, diffuse-type 0/17                                             park  
hepatocellular w/HCV 9/22       3 1       3       1       2           huang independent mutations in same tumor
hepatocellular 12/35       1 1 2 1 1       1 2       2   1       Van Nhieu multiple independent/coreelates with poorer prognosis
hepatocellular 6/26       2   1     1               1           De La Coste  
hepatocellular 14/75       5 1 1             1       4           miyoshi  
hepatocellular 21/119       3 3 1 1   2       4       8           legoix multiple independent mutations in some tumor/ inverse correlation with LOH
hepatoblastoma, sporadic 8/9           2     1               1           jeng  
hepatoblastoma, sporadic 27/52       2   3     1       5                   koch no APC mutations
hepatoblastoma 12/18       2   1             1       1           wei overlap with Beckwith-Wiedemann
kidney, Wilms' tumor 6/40                         1       2          

koesters

Maiti, 2000

overlap with WT1 mutations
medulloblastoma, sporaic 3/67         2       1                           zurawel no GSK3b mutations
melanoma 1/65                                 1              
ovarian, endometriod 7/13       3 1       2       1                   gamallo mutation corellated with better prognosis
ovarian, endometriod 3/11                 2       1                   palacios  
ovarian, endometriod 10/63         2 2     6                           wright 3 also contain PTEN mutations / more frequent in low grade
pancreatic tumors 0/111                                             ramaswamy  
pilomatricoma 12/16       2 4 3     2       1                   chan  
prostate cancer 5/104       1 2               1       1           voeller focal based on microdissection
thyroid, anaplastic 19/31         1     1 3 1   8 2 1 1 4 2 1 2   9   garcia-rostan multiple independent mutations in some tumors
uterine endometrium 10/76         1       2       4       3           fukuchi mutations more common in low grade cancers