Table 3 APC truncation mutation profiles.

From: A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC

No. of APC Mutations*

     

Zones 1–2

Zones 3–4

N

MSI

Loss

Allelic WNT †

Other remaining

0

0

156

45

0

36

75

0

1

130

3

46

35

44

1

0

57

4

13

17

24

2

0

7

2

0

3

2

0

2

8

0

2

2

6

1

1

105

6

8

22

67

1

2–3

2§

0

0

2

0

2

1

3§

1

0

1

1

Total

 

468

61

69

118

219

  1. APC, Adenomatous polyposis coli; Mets, metastasis; MSI, microsatellite instability.
  2. *zones 1–2 include APC codons 1–1,262; zones 3–4 include APC codons 1,263–2,843. Also see Supplementary Table 5.
  3. †The mutations were tabulated only for cases that had neither MSI nor allelic loss. Other WNT pathway mutations included the following: CTTNA1, CTNNB1, CTTND2, WNT1, WNT2, WNT2B, WNT4, WNT9B, WNT10B, AMER1, TCF7L2, MACF1, AXIN1, WIF1, GSK3B and CDH1.
  4. In all seven samples, one of the mutations was in a variant isoform of APC (not the canonical isoform NM_0001127511), which we believe does not violate the prevailing theory that at least one functional 20-amino-acid β-catenin-binding site27 is needed, as we expect that the canonical APC isoform will sometimes be translated into protein by the tumour, which have some functional binding sites. This is consistent with the reduced impact of other APC alternative splice-variant mutations61.
  5. §These five samples have more than the two truncation mutations. Thus, at least two of the APC mutations reside on the same allele. Again, consistent with the prevailing theory, we infer that the three cases with two zone 1–2 hits reside on the same allele and two of these cases are hypermutated POLE tumours.
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