Cell biology & cancer genetics — MRCP Part 1 flashcards

Question 1

How many alleles of a tumour suppressor gene must be inactivated to cause cancer, and what is this principle called?

Accepted Answer

Both alleles: Knudson's two-hit hypothesis. — Tumour suppressors act through loss of function; oncogenes need only one activated allele (gain of function).

Question 2

A woman with Li-Fraumeni syndrome (germline TP53 mutation) asks about cancer surveillance. Which imaging is used, and what exposure should be avoided?

Accepted Answer

Regular MRI-based surveillance (whole-body, brain and breast MRI); avoid unnecessary ionising radiation (CT, radiotherapy where possible). — TP53 (chromosome 17) is the 'guardian of the genome'; carriers have a very high lifetime cancer risk and are prone to radiation-induced cancers.

Question 3

A germline activating mutation of which proto-oncogene predisposes to medullary thyroid cancer?

Accepted Answer

RET (a receptor tyrosine kinase). — RET mutations underlie MEN2A/2B and familial medullary thyroid cancer.

Question 4

Which tumour suppressor protein acts as the brake at the G1/S checkpoint, and which kinase complex releases it?

Accepted Answer

Retinoblastoma (Rb) protein; it is released when phosphorylated by cyclin D–CDK4/6. — Unphosphorylated Rb holds the E2F transcription factors; once Rb is phosphorylated, E2F drives the cell into S phase. G1/S is the most important checkpoint.

Question 5

A 30-year-old man has chronic sinusitis, bronchiectasis and infertility. His chest X-ray shows dextrocardia. Which component of his cilia is defective?

Accepted Answer

The dynein arms (primary ciliary dyskinesia, Kartagener syndrome). — Dynein is the motor that bends the 9+2 microtubule axoneme. Immotile cilia cause poor mucus clearance; immotile sperm cause infertility; situs inversus occurs in about half.

Question 6

Southern blot detects ______, Northern blot detects RNA, and Western blot detects protein.

Accepted Answer

DNA — Each technique separates molecules on a gel and then uses a labelled probe (DNA/RNA) or antibody (protein) to find the target.

Question 7

Southern blot detects DNA, Northern blot detects RNA, and Western blot detects ______.

Accepted Answer

protein — Each technique separates molecules on a gel and then uses a labelled probe (DNA/RNA) or antibody (protein) to find the target.

Question 8

What type of point mutation causes sickle cell disease?

Accepted Answer

A missense mutation: glutamic acid is replaced by valine at position 6 of the beta-globin chain. — One base change alters one amino acid; HbS polymerises when deoxygenated, sickling the red cells.

Question 9

What type of mutation is F508del (ΔF508), the commonest cystic fibrosis mutation?

Accepted Answer

An in-frame deletion: three nucleotides are lost, removing one phenylalanine at position 508 without shifting the reading frame. — The misfolded CFTR protein is mostly degraded before it reaches the cell membrane.

Question 10

Burkitt lymphoma overexpresses ______ through t(8;14), whereas mantle cell lymphoma overexpresses cyclin D1 through t(11;14).

Accepted Answer

c-MYC — Both translocations move the oncogene next to the immunoglobulin heavy-chain locus on chromosome 14, switching it on in B cells.

Question 11

Burkitt lymphoma overexpresses c-MYC through t(8;14), whereas mantle cell lymphoma overexpresses ______ through t(11;14).

Accepted Answer

cyclin D1 — Both translocations move the oncogene next to the immunoglobulin heavy-chain locus on chromosome 14, switching it on in B cells.

Question 12

Germline mutation of which tumour suppressor gene causes clear cell renal carcinoma, CNS haemangioblastomas and phaeochromocytoma?

Accepted Answer

VHL (von Hippel–Lindau gene, chromosome 3p). — Loss of VHL stabilises HIF, switching on angiogenic genes such as VEGF, which explains the highly vascular tumours.

Cell biology & cancer genetics flashcards

More Basic sciences & statistics topics