Targets & Mechanisms: Passenger mutations take the wheel

 

Table 1. Potentially targetable passenger mutations in cancer. Two papers, one published in Nature and the other in Cell, identified
mutations that occur in genes involved in the cellular housekeeping and metabolic functions of tumor cells. Below are the top hits.

Muller et al.

Gene abbreviation

Encoded protein

Cellular pathway

ENO1

Enolase 1α

Glycolysis and gluconeogenesis

H6PD

Hexose-6-phosphate dehydrogenase

Pentoase phosphate shunt

KIF1B

Kinesin family member 1B

Chromosomal segregation

NMNAT1

Nicotinamide nucleotide adenylyltransferase 1

Nicotinamide dinucleotide (NAD) biosynthesis

UBE4B

Ubiquitination factor E4B

Ubiquitin-dependent degradation

ACO1 (IRP1)

Aconitase 1

Iron metabolism and citric acid cycle

KLHL9

Kelch-like 9

Chromosomal segregation

PANK1

Pantothenate kinase 1

Acetyl-CoA biosynthesis

KIF20B

Kinesin family member 20B

Chromosomal segregation

Nijhawan et al.

Gene abbreviation

Encoded protein

Cellular pathway

PSMC2

Proteasome 26S subunit ATPase 2

Proteasome-mediated degradation

EIF2B2

Eukaryotic translation initiation factor 2B subunit 2b

Protein synthesis

EEF2

Eukaryotic translation elongation factor 2

Protein synthesis

PHF5A

PHD finger protein 5A

Spliceosome-mediated mRNA splicing

HPGD (15-PGHD)

Hydroxyprostaglandin dehydrogenase 15 NAD

Prostaglandin metabolism

RPS15

Ribosomal protein S15

Component of 40S ribosome subunit

SNRPB

Small nuclear ribonucleoprotein polypeptides B and B1

Pre-mRNA splicing

POLR2F

Polymerase RNA II DNA-directed polypeptide F

Component of RNA polymerase

USPL1

Ubiquitin-specific peptidase-like 1

Ubiquitin-dependent degradation