β-catenin mutations in human cancers
updated Sept 1, 2000
β-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.
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 | 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 |
