2 genetic molecular and cellular basis of cancer Flashcards
How many different types of cancer are there?
here are approximately 200 different types of cancer.
What percentage of cancer cases in the UK are due to breast, lung, bowel, and prostate cancer?
These four cancers account for over 50% of cases.
What is the lifetime risk of being diagnosed with cancer?
One in two people will be diagnosed with cancer in their lifetime.
How does age affect cancer risk?
Cancer risk rises significantly with age, with ~65% of cases occurring in people over 65.
How is cancer defined?
Cancer is a heterogeneous group of diseases in which single cells acquire the ability to proliferate abnormally, leading to an accumulation of progeny.
What is the difference between a tumour and cancer?
Tumours are abnormal cell growths, while cancers are tumours that have acquired the ability to invade surrounding tissues and potentially metastasise.
What is metastasis?
Metastasis is the process where cancer cells escape their original location, travel through blood or lymphatic systems, and form secondary tumours in distant sites.
Why is cancer considered a genetic disease?
Cancer results from genetic mutations that affect key biological processes like cell division, invasion, and metastasis.
Why is cancer common at the individual level but rare at the cellular level?
At the cellular level, multiple mutations are needed for cancer to develop, and protective mechanisms (e.g., DNA repair, apoptosis) help prevent it.
Why is cancer development a multi-step process?
Multiple successive mutations (~6-7) are needed to overcome cellular defences and drive malignant transformation.
What is the difference between benign and malignant tumours?
Benign tumours are localised and non-invasive, while malignant tumours can invade tissues and metastasise.
What methods are used to classify cancers?
Cancer classification is based on histology (tissue architecture and cellular morphology), genetic markers, and expression profiles.
What is angiogenesis?
Angiogenesis is the formation of new blood vessels to supply nutrients and oxygen to tumours, enabling their growth beyond 1mm.
How do tumours promote angiogenesis?
Tumours produce factors that trigger blood vessel formation, promoting proliferation, invasion, and differentiation of capillaries.
What is the primary cause of death in cancer patients?
Metastasis, as secondary tumours are often resistant to treatments targeting primary tumours.
What is the mutational theory of cancer?
Cancer arises due to mutations that accumulate over time, leading to uncontrolled cell growth.
What types of genetic mutations are associated with cancer?
Cancer-related mutations include chromosome number changes, translocations, amplifications, small deletions, insertions, single base mutations, and epigenetic changes.
What role do viruses play in cancer?
Some viruses (e.g., HPV, EBV, hepatitis viruses, HIV) introduce exogenous sequences that contribute to cancer development.
Why is cancer rare at the cellular level?
Cells have DNA repair mechanisms, apoptosis, and other protective features that prevent single mutations from causing cancer.
What are oncogenes?
Oncogenes are mutated genes that promote excessive cell proliferation, growth, and invasion, leading to cancer.
What is a proto-oncogene?
A proto-oncogene is a normal gene that regulates cell growth but can become an oncogene if mutated.
What are tumour suppressor genes?
they inhibit processes leading to cancer by regulating the cell cycle, promoting apoptosis, and maintaining genomic stability.
: What is Knudson’s two-hit hypothesis?
It suggests that two mutations (one in each allele) are required to inactivate tumour suppressor genes and drive cancer progression.
Why does cancer develop over multiple steps?
Multiple successive genetic errors (~6-7 mutations) are needed to bypass normal cell defences and drive malignant transformation.
What is clonal evolution in cancer?
It refers to the accumulation and selection of multiple mutations that increase a cell’s growth advantage over time.
What are the two main effects of cancer-related mutations?
(1) Increased cell growth, division, and survival; (2) Increased genomic instability, leading to more mutations.
How do malignant colorectal tumours develop?
They arise from benign adenomas through sequential mutations that activate oncogenes and inactivate tumour suppressor genes.
Do all colorectal tumours have the same mutations?
No, only about 50% have K-RAS mutations, while other mutations vary between tumours.
How does the order of mutations affect tumour development?
The sequence of mutations can impact tumour progression, e.g., some early K-RAS mutations do not always lead to cancer.
What is clonality in cancer?
Cancer often arises from a single mutated cell that proliferates abnormally, giving rise to genetically identical tumour cells.
Why do cancers with high mutation rates evolve rapidly?
Increased mutations enhance diversity, enabling cancer cells to adapt, resist treatments, and metastasise.
Why is cancer classification important for treatment?
Proper classification helps determine the most effective therapy based on the tumour’s histology, genetic profile, and stage.
Why are metastatic cancers harder to treat?
Metastases may have different mutations from the primary tumour and often resist standard treatments.
What is the role of angiogenesis inhibitors in cancer treatment?
These drugs block new blood vessel formation, starving tumours of oxygen and nutrients.
Why are tumour suppressor gene mutations harder to target therapeutically?
Unlike oncogenes (which are activated), tumour suppressors lose function, making it difficult to restore their activity with drugs.
What are the three main mechanisms of oncogene activation in cancer?
Gene amplification – Increased copies of an oncogene (e.g., MYC, HER2).
Chromosomal translocation – Fusion with another gene, leading to abnormal expression (e.g., BCR-ABL in CML).
Point mutations – Changes in DNA sequence that increase oncogene activity (e.g., RAS mutations).
Why are oncogenes considered dominant mutations?
Because only one allele needs to be mutated for a gain-of-function effect.
What are the mechanisms of tumour suppressor gene (TSG) inactivation?
Gene deletion – Entire TSG or surrounding region is lost.
Truncating mutations – Frameshift, nonsense mutations introduce premature stop codons (e.g., APC in colorectal cancer).
Missense mutations – Change in amino acids affecting protein function (e.g., P53 mutations).
Epigenetic silencing – DNA hypermethylation of promoter regions turns off TSG expression (e.g., MLH1 in Lynch Syndrome).
What is a dominant-negative mutation?
A mutant protein interferes with the function of the normal protein, such as mutant P53 preventing the normal protein from binding DNA.
What are the two major models of cancer evolution?
Clonal evolution model – Mutations accumulate, and more aggressive clones outcompete others.
Hierarchical cancer model – A small population of cancer stem cells drives tumour growth, while most cells lack self-renewal capacity.
Why do cancers with high mutation rates evolve rapidly?
High mutation rates create genetic diversity, allowing subclones to adapt to treatments and new environments (e.g., drug resistance).
Do all tumours follow the same progression model?
No, cancers can take alternative genetic pathways to malignancy. Not every tumour acquires the same set of mutations.
How does colorectal cancer demonstrate alternative progression routes?
While the traditional model involves APC loss → KRAS activation → P53 loss, some tumours bypass KRAS mutation and develop through different genetic events.
How do DNA repair defects increase cancer risk?
Mutations in DNA repair genes lead to genomic instability, increasing the chance of oncogene activation and TSG loss.
What is Lynch Syndrome, and how is it related to cancer?
Lynch Syndrome is caused by mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2), leading to an increased risk of colorectal and other cancers.
What are the six classical hallmarks of cancer described by Weinberg and Hanahan?
Sustaining proliferative signalling (e.g., oncogenes like RAS).
Evading growth suppressors (e.g., RB, P53 loss).
Resisting cell death (e.g., BCL-2 overexpression).
Enabling replicative immortality (e.g., telomerase activation).
Inducing angiogenesis (e.g., VEGF signalling).
Activating invasion and metastasis (e.g., E-cadherin loss)
What are two emerging hallmarks of cancer?
Deregulating cellular metabolism – Cancers switch to aerobic glycolysis (Warburg effect).
Evading immune destruction – Tumours avoid immune detection (e.g., PD-L1 expression).
How does genomic instability contribute to cancer progression?
Mutations in DNA repair genes (e.g., BRCA1, MLH1) lead to increased mutation rates, allowing further oncogene activation and tumour suppressor loss, creating a feedback loop that accelerates cancer development.
How do oncogene mutations differ from tumour suppressor gene mutations?
oncogenes
normal function: promote cell growth
mutation type: gain-of-function
no. of alleles affected: one (dominant)
e.g.: RAS, MYC, HER2
TSG
normal: suppress uncontrolled growth
mutation: loss-of-function
no of alleles affected: two (recessive)
e.g.: p52, RB1, BRCA1
