Table 1 Overview of genetic and epigenetic abnormalities in MM that induce or facilitate canonical Wnt activation

From: Aberrant Wnt signaling in multiple myeloma: molecular mechanisms and targeting options

Gene

CDS change

AA change

Mutation type

Clinical significance

Recurrence

Frequency

Classic Wnt pathway mutations [44,45,46,47,48]

      

APC

nr

S1465fs

Frameshift

Pathogenic

Recurrent in CRC

1/133

APC

6976C>G

R2326G

Missense

Likely pathogenic

Germline mutation in FAP

1/84

APC

718A>T

T240S

Missense

Unknown

Not previously reported

1/84

APC

5369G>A

R1790K

Missense

Unknown

Not previously reported

1/14

APC

497insAa

T166fs

Frameshift

Pathogenic

Not previously reported

nr

AXIN1

2089C>T

P697S

Missense

Likely pathogenic

Sporadic in HCC

1/203

AXIN2

944C>T

T315M

Missense

Likely pathogenic

Sporadic in GC

1/203

CTNNB1

nr

T41I

Missense

Pathogenic

Recurrent in CRC and PC

1/133

RSPO/LGR4/RNF43/ZNRF3 mutations [46]

RSPO2

219G>T

E73D

Missense

Unknown

Not previously reported

1/203

RSPO2

257G>A

R86Q

Missense

Likely pathogenic

Recurrent in CRC and PC

1/203

RNF43

1813G>T

A605S

Missense

Unknown

Not previously reported

1/203

RNF43

1976delG

G659fs

Frameshift

Pathogenic

Recurrent in CRC and PC

1/203

ZNRF3

2419G>C

A807P

Missense

Unknown

Not previously reported

1/203

ZNRF3

68T>G

V23G

Missense

Unknown

Not previously reported

1/203

Promotor methylation of secreted Wnt antagonists [61, 62, 65]

 

Abnormalities in LGR4 [63]

Gene

pMM

HMCLs

 

mRNA overexpression

86% (30/35)

 

APC

18% (9/50)

25% (1/4)

    

WIF

22% (11/50)

50% (2/4)

 

Abnormalities in CYLD [44,45,46,47,48, 68,69,70]

  

DKK1

33% (3/12)

67% (4/6)

 

Mutation

3% (22/744)

 

DKK3

16% (8/50)

50% (2/4)

 

Deletion

17% (nr/nr)

 

sFRP1

27% (33/123)

78% (7/9)

 

16q deletion

35% (40/114)

 

sFRP2

52% (38/73)

56% (5/9)

    

sFRP3/FRZB

nd

nd

 

Abnormalities in BCL9 [69, 72, 78,79,80]

sFRP4

7% (8/123)

56% (5/9)

 

mRNA overexpression

60% (38/64)

 

sFRP5

6% (7/123)

67% (6/9)

 

Low miR30 expression

60% (47/78)

 
    

1q gain

36% (192/530)

 
  1. Clinical significance and recurrence is based on previous publications on these specific mutations and/or occurrence of these mutations in the Catalog of Somatic Mutations in Cancer (COSMIC) database (www.cancer.sanger.uc.uk)
  2. CDS coding DNA sequence, AA amino acid, nr not reported
  3. aPatient with germline mutation in APC (attenuated form of familial adenomatous polyposis) that developed MM
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