Pathology Cheat Sheet
Growth Without Restraint
Molecular basis of cancer for NEET-PG: oncogenes, RAS, BCR-ABL, two-hit hypothesis, RB and p53, telomerase, aflatoxin, HPV E6 and E7, and carcinogenesis stages.
MedNext Academy | 3 min read
Growth Without Restraint
Molecular basis of cancer for NEET-PG: oncogenes, RAS, BCR-ABL, two-hit hypothesis, RB and p53, telomerase, aflatoxin, HPV E6 and E7, and carcinogenesis stages.
The molecular basis of cancer through oncogenes and tumour suppressors, and the multistep process of chemical, radiation and viral carcinogenesis.
High-yield lines
- Proto-oncogenes promote growth, and gain-of-function mutation of a single allele converts them to oncogenes.
- RAS point mutation locks the protein in its active GTP-bound state and is the most common oncogene mutation in human cancers.
- The Philadelphia chromosome t(9;22) creates the BCR-ABL1 fusion tyrosine kinase driving chronic myeloid leukaemia.
- The t(8;14) translocation drives MYC overexpression in Burkitt lymphoma.
- Tumour suppressor genes restrain growth, and the Knudson two-hit hypothesis requires inactivation of both alleles.
- RB1 loss removes the G1 to S checkpoint, and the retinoblastoma protein normally inhibits E2F transcription factors.
- TP53, the guardian of the genome, is the most commonly mutated gene in human cancer and triggers arrest or apoptosis after DNA damage.
- Telomerase reactivation grants replicative immortality in over ninety percent of cancers.
- Chemical carcinogenesis follows initiation, promotion, and progression, where initiation is an irreversible DNA mutation and promotion is reversible clonal expansion.
- Aflatoxin B1 causes a specific TP53 codon 249 mutation and hepatocellular carcinoma, synergising with hepatitis B.
- Aromatic amines cause bladder urothelial carcinoma, vinyl chloride causes hepatic angiosarcoma, and benzene causes acute myeloid leukaemia.
- HPV E6 degrades p53 and E7 inactivates Rb, driving cervical carcinoma, while EBV is linked to Burkitt and nasopharyngeal carcinoma.
Mapped competency codes
- PA7.2
- PA7.3
Continue into the full chapter
This summary maps to PA7-neoplastic-disorders.
Frequently Asked Questions
What is the Knudson two-hit hypothesis?
It states that both alleles of a tumour suppressor gene must be inactivated for its protective function to fail, which explains earlier tumour onset in inherited cancer syndromes.
Which oncogene is created by the Philadelphia chromosome?
The BCR-ABL1 fusion gene from t(9;22), which encodes a constitutively active tyrosine kinase that drives chronic myeloid leukaemia.
How do HPV oncoproteins cause cancer?
E6 binds and degrades p53 while E7 binds and inactivates Rb, disabling both major tumour suppressor pathways and driving uncontrolled proliferation.
What cancer is caused by aflatoxin B1?
Hepatocellular carcinoma, through a characteristic TP53 codon 249 mutation, with a synergistic effect in patients also infected with hepatitis B virus.
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