STEPTRACKERCROSS-SYSTEM | GENETICS + ONCOLOGY | RAPID-FIRE REVIEW

Gene & Translocation Master Table

The high-yield oncogenes, tumor suppressors and translocations in one place — what each gene does and where it shows up.

FOCUS ON
Oncogenes need one gain-of-function hit (RAS, MYC, BCR-ABL, RET, BRAF). Tumor suppressors need two hits (RB1, TP53, APC, VHL, NF1, BRCA). Translocations either make a fusion protein (BCR-ABL, PML-RARA, EWSR1-FLI1) or place an oncogene next to an immunoglobulin promoter (MYC, BCL2, cyclin D1).
GENE · TRANSLOCATION
ACTION
DISEASE
PAGE
t(9;22) BCR-ABL
oncogene fusion
Constitutive tyrosine kinase
CML; some ALL (worse)
Imatinib · 6.03
t(15;17) PML-RARA
Blocks differentiation at promyelocyte
Acute promyelocytic leukemia (DIC)
ATRA · 6.02
t(8;14) MYC–IgH
MYC driven by Ig heavy-chain promoter
Burkitt lymphoma (starry sky)
6.11
t(14;18) IgH–BCL2
Antiapoptotic BCL2 overexpressed
Follicular lymphoma
6.06
t(11;14) cyclin D1–IgH
Cell-cycle G1→S push
Mantle cell lymphoma
6.11
t(11;18) API2-MALT1
NF-κB activation
Gastric MALT lymphoma resistant to H pylori therapy
10.04
JAK2 V617F
Cytokine-independent signaling
Polycythemia vera, essential thrombocythemia, myelofibrosis
6.04
t(11;22) EWSR1-FLI1 · t(X;18) SS18-SSX · t(2;13) PAX3-FOXO1
Fusion transcription factors
Ewing · synovial sarcoma · alveolar rhabdomyosarcoma
17.10
KRAS
GTPase stuck "on"
Pancreatic (earliest), colorectal, lung adenocarcinoma
Blocks anti-EGFR benefit · 11.02
BRAF V600E
MAPK kinase activation
Melanoma, papillary thyroid, hairy cell leukemia, LCH, serrated colon lesions
18.04
EGFR · ALK · HER2
Receptor tyrosine kinases
Lung adenocarcinoma (non-smokers) · breast, gastric (HER2)
TKIs, trastuzumab · 9.10
RET
Receptor tyrosine kinase (gain of function)
MEN2A/2B, medullary thyroid; RET/PTC in papillary thyroid
15.11
KIT
Receptor tyrosine kinase
GIST, mastocytosis, acral melanoma, seminoma
Imatinib · 10.13
MYCN · IDH1/2
Transcription factor · oncometabolite 2-HG
Neuroblastoma · glioma, chondrosarcoma, AML
16.11
RB1
tumor suppressor
Holds E2F; blocks G1→S
Retinoblastoma, osteosarcoma
17.05
TP53
Guardian of the genome; arrest or apoptosis
Most cancers; Li-Fraumeni (sarcoma, breast, brain, adrenal)
16.13
APC · MLH1/MSH2
β-catenin degradation · mismatch repair
FAP, colorectal cancer · Lynch syndrome
10.12
BRCA1 · BRCA2
Homologous recombination repair
Breast, ovarian (BRCA1) · male breast, pancreas, prostate (BRCA2)
PARP inhibitors · 13.11
VHL · NF1 · NF2 · TSC1/2
HIF degradation · RAS-GAP · merlin · mTOR brake
RCC, hemangioblastoma · neurofibromas · schwannomas · hamartomas
16.13
WT1 · MEN1 · PTEN · CDKN2A
Kidney development · menin · PI3K brake · p16 (CDK inhibitor)
Wilms · MEN1 · Cowden, endometrial · melanoma, pancreatic
12.12
SMAD4 · STK11 · PTCH1 · CDH1
TGF-β signal · LKB1 kinase · hedgehog brake · E-cadherin
Pancreatic, juvenile polyposis · Peutz-Jeghers · BCC, Gorlin · diffuse gastric, lobular breast
10.11

Mechanism — one hit or two

Proto-oncogeneAccelerator
→
One activating mutationDominant (gain of function)
Tumor suppressorBrake
→
First hitInherited or somatic
→
Second hitLoss of heterozygosity → tumor

Inherited cancer syndromes are usually autosomal dominant at the family level, yet recessive at the cell level (both alleles must be lost).

Translocation types

TYPE
MECHANISM
EXAMPLES
Fusion protein
Two genes joined into a new protein
BCR-ABL, PML-RARA, EWSR1-FLI1, SS18-SSX
Promoter swap
Oncogene placed under a strong Ig promoter
MYC t(8;14), BCL2 t(14;18), cyclin D1 t(11;14)
Amplification
Extra copies of an oncogene
HER2, MYCN, MDM2, L-MYC
Point mutation
Single-base gain of function
KRAS, BRAF V600E, JAK2 V617F

How it's tested

COMMON CONFUSIONt(14;18) (follicular, BCL2, antiapoptotic) vs t(8;14) (Burkitt, MYC, proliferation) vs t(11;14) (mantle cell, cyclin D1) — all use chromosome 14's IgH locus.
THE TRAPA targeted drug only works when its target is driving the tumor: anti-EGFR antibodies fail with KRAS mutation; BRAF inhibitors need BRAF V600E.
YOUR APPROACHTumor → driver gene → oncogene or suppressor → inheritance pattern → targeted drug or screening plan.

If you see… think…

Philadelphia chromosome → t(9;22) BCR-ABL (CML)
Leukemia with DIC treated with vitamin A derivative → t(15;17) APL
Starry-sky lymphoma in a child's jaw or ileum → t(8;14) MYC (Burkitt)
Indolent lymphoma with BCL2 overexpression → t(14;18) follicular
Polycythemia with low EPO → JAK2 V617F
Earliest mutation in pancreatic cancer → KRAS
Bilateral retinoblastoma, later osteosarcoma → germline RB1
Family with sarcomas, breast and brain tumors at young ages → TP53 (Li-Fraumeni)
Lobular breast cancer and diffuse gastric cancer in one family → CDH1
Poor-prognosis neuroblastoma → MYCN amplification