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. 2019 Sep 19;2(3):680–709. doi: 10.20517/cdr.2019.006

Table 3.

Germline (G) and somatic (S) mutations affecting coding (c) and non-coding (nc) regions of genes coding phase I enzyme in primary liver cancer

Gene Protein Genetic mutations G/S Region Protein mutations Functional consequences Clinical consequences Studies References
DPYD DPD c.1700G >T S c Gly567Val       Moderate Pathogenic TCGA-LIHC     TCGA
c.589C>T S c Pro197Ser       Moderate Pathogenic TCGA-LIHC     TCGA
c.491A>C S c Lys164Thr       Moderate ND TCGA-LIHC     TCGA
c.*102A>C S   nc 3’ UTR       Modifier ND TCGA-LIHC     TCGA
c.483+820G>C S   nc Intron       Modifier ND TCGA-LIHC     TCGA
DPYS DHP c.650A>T S c His217Leu       Moderate ND TCGA-LIHC     TCGA
CYP2D6 CYP2D6 c.100C>T S c Pro34Ser       High Increased HCC susceptibility Cirrhotic / Fibrotic HCC patients     [79]
CYP2C9 CYP2C9 c.1075A>C S c Ile359Leu       High ND Cirrhotic / Fibrotic HCC patients     [79]
CYP2A6 CYP2A6 c.715C>G S c Gln239Glu       Moderate ND TCGA-LIHC     TCGA
c.323A>G S c Asp108Gly       Moderate Neutral TCGA-LIHC     TCGA
c.*527C>G S   nc 3’ UTR       Modifier ND TCGA-LIHC     TCGA
c.*135A>G S   nc 3’ UTR       Modifier ND TCGA-LIHC     TCGA
c.194+409A>G S Intron       Modifier ND TCGA-LIHC     TCGA
CYP3A4 CYP3A4 c.-59A>G S   nc 5´ UTR       Modifier ND TCGA-LIHC     TCGA
CES2 CES c.278C>G S c Ser93*       High ND TCGA-LIHC     TCGA
c.1524G>A S c Trp508*       High Neutral TCGA-LIHC     TCGA
c.153G>T S c Gln51His       Moderate ND TCGA-LIHC     TCGA
EH EH c.337T>C S c Tyr113His       Low Increase risk of HCC HCC patients     [81]
c.416A>G S c His139Arg       High ND HCC patients     [81]
NQO1 NQO1 c.127T>G S c Tyr43Asp       Moderate ND TCGA-LIHC     TCGA

Data obtained from TCGA database and referred literature. Functional consequences are based on VEP (Variant Effect Predictor; https://www.ensembl.org/vep) impact: High means that the variant is supposed to cause a high disruptive impact in the protein, which is likely to cause loss of function; Moderate means that the variant may be not disruptive, but results in a decrease effectiveness of the encoded protein; Low means that the variant has low probability to cause a disruptive change in the encoded protein; Modifier is usually referred to non-coding variants, whose impact is difficult to determine, although they can be involved in transcription or splicing changes. HCC: hepatocellular carcinoma; ND: not described; TCGA: the cancer genome atlas; TCGA-LIHC: the cancer genome atlas - liver hepatocellular carcinoma