In a cell culture dish, a researcher

studies medulloblastoma cells derived from a patient with PTCH

loss-of-heterozygosity (LOH). When treated with a SMO inhibitor, most cells in

culture die initially. After several weeks, in the presence of the inhibitor, a

small number of  cells begins to

proliferate rapidly. Molecular analysis reveals that the Hedgehog pathway is

reactivated despite drug treatment.

Which explanation best accounts for

the observed drug resistance?

A patient with HER2-positive

metastatic breast cancer initially responds to trastuzumab therapy, with tumor

shrinkage observed on imaging. After six months, the tumor begins to regrow. A

biopsy of the recurrent tumor shows that the HER2 receptor is still expressed

but lacks the extracellular domain necessary for antibody binding, and

downstream MAPK/PI3K signalling remains active.

Which mechanism best explains the

observed resistance to trastuzumab?

In

an experimental cancer model, investigators inhibit vascular development using

targeted genetic and drug-based approaches. As a result, the tumour is unable

to establish new blood vessel networks. Although the tumour cells remain alive,

their size and progression differ markedly from tumours with intact

vasculature.

Which

tumour property is most immediately constrained when angiogenesis is

suppressed?

Researchers are studying melanoma

cells that initially respond to vemurafenib. Over time, some cells develop

resistance. Sequencing reveals a p61 B-RAF(V600E) splice variant lacking a

portion of the regulatory domain. Western blot analysis shows that MEK

phosphorylation remains high even in the presence of the inhibitor.

Which explanation best accounts for

these findings?

A child inherits one mutated copy of

the RB transcriptional corepressor 1 (RB1) gene from a parent but does not

initially develop cancer. Later, a retinal cell acquires a second mutation in

the remaining RB1 allele, and the cell begins to proliferate uncontrollably.

What principle of cancer genetics does

this example best illustrate?

A researcher studying bacteria exposed

to UV radiation observes that cells survive only if they possess functional

UvrA, UvrB, and UvrC proteins. Mutants lacking these proteins accumulate DNA

lesions and fail to repair the damage.

Which explanation best accounts for

this observation?

A

cancer sequencing profile shows that a patient carries a germline pathogenic

variant in a classical tumour suppressor gene, across all normal tissues. In

the tumour sample, the remaining wild‑type allele is absent due to a somatic

loss‑of‑heterozygosity event.

Which

statement BEST reflects how tumour suppressor genes contribute to oncogenesis?

Next generation sequencing of tumour

samples of rapidly proliferating cells from lung cancer patients identify

several missense mutations in the EGFR gene. Functional studies show that these

mutant receptors signal even when no growth factor is present.

Which statement BEST explains how

these EGFR mutations contribute to cancer?

Duchenne Muscular dystrophy (DMD) can be caused by a mutation leading to the exclusion of exons 49 and 50 of the dystrophin gene (exon pattern illustrated below). 

Which of the following proposed antisense oligonucleotide (ASO) treatment would likely be most effective for patients with this mutation, to allow them to produce some functional dystrophin protein?

A paediatric

patient is enrolled in an experimental gene therapy trial for a genetic disease

caused by loss of function in a very large protein. Because the full-length

coding sequence exceeds the packaging capacity of adeno-associated virus (AAV)

vectors, researchers divide the gene into two separate vectors and incorporate

intein sequences to restore protein function after delivery.

What

makes inteins especially valuable for this gene therapy strategy?