WK1: types of cancer, mutations and viral carcinogens

What are the 4 main types of cancer by cell origin?

Carcinomas (85%) Sarcomas (12%) Lymphomas (3%) Leukaemias (3%).

What is the difference between benign and malignant tumours?

Benign = abnormal growth but does NOT invade surrounding tissues or metastasise. Malignant = poorly differentiated cells that grow rapidly can invade tissues and metastasise.

What are carcinomas? Give 3 examples.

Carcinomas arise from epithelial cells that cover external and internal body surfaces. They account for 85% of cancers. Examples: lung breast colon.

What is adenocarcinoma?

A subtype of carcinoma that arises from glandular epithelial tissue.

What are sarcomas and where do they originate?

Sarcomas (~12% of cancers) originate from mesenchymal layer cells (supporting tissues: bone cartilage fat connective tissue muscle). They are highly malignant.

What is the difference between lymphomas and leukaemias?

Lymphomas = solid cancers arising in lymph nodes and immune tissues (B T NK cells). Leukaemias = "liquid" cancers of immature white blood cells that proliferate in bone marrow and accumulate in bloodstream.

What is the difference between staging and grading of cancer?

Staging = how far cancer has spread (TNM: tumour size lymph nodes metastasis). Grading = how abnormal cells look under microscope (Grade I-II = fewer abnormalities; Grade III-IV = more abnormalities).

What are the 3 main causes of DNA mutations?

1) Mistakes in DNA replication (misincorporation of deoxynucleotides). 2) Spontaneous chemical changes to nucleotides. 3) Mutagenic agents (physical: UV/X-rays; chemical: vinyl chloride nitrosamines).

What is the 4th cause of DNA mutations mentioned in the lecture?

Viruses (e.g. HBV EBV HPV).

What are the 4 types of DNA lesions/repair examples from the table?

1. Incorrect base (proofreading error).

2. Missing base (base excision repair).

3. Strand breaks (ionising radiation).

4. Linked pyrimidines (UV radiation).

5. Cross-linked strands (alkylating agents like vinyl chloride).

What is Xeroderma Pigmentosum (XP)?

A hereditary cancer syndrome with defects in nucleotide excision repair. Patients cannot repair UV-induced DNA damage leading to high risk of skin cancers.

What is Li-Fraumeni syndrome and which gene is involved?

Caused by TP53 mutation. Patients develop multiple cancer types (breast sarcoma leukaemia etc.). TP53 is the "guardian of the genome".

What is the difference between how DNA viruses and RNA viruses cause cancer?

DNA viruses (HPV EBV HBV) = viral genome persists as an episome (circular DNA) and promotes proliferation or inhibits tumour suppressors. RNA viruses (HCV HTLV1) = retrotranscribed into DNA and integrated as a provirus into host genome.

What are the two mechanisms by which RNA viruses cause cancer?

1) Provide an oncogene (extra growth gene). 2) Insertional mutagenesis (virus integrates near host growth gene and upregulates its expression).

What is the difference between direct and indirect viral carcinogenesis?

Direct = virus acts from within the cell that will form the tumour; virus found in monoclonal form in tumour cells. Indirect = virus acts from outside the cell that will form the tumour. Most tumour viruses use both.

Match: HPV / HBV / HCV / EBV to their associated cancers.

HPV = cervical carcinoma. HBV = hepatocellular carcinoma (liver). HCV = hepatocellular carcinoma (liver). EBV = Burkitt's lymphoma and nasopharyngeal carcinoma.

Which two oncogenic viruses do NOT carry their own oncogenes?

HBV and HCV (unlike most other oncoviruses like HPV and EBV).

Which virus is associated with Kaposi's sarcoma?

HHV-8 (also called KSHV – Kaposi's sarcoma herpesvirus).

Which virus is associated with T-cell lymphoma?

HTLV-1 (a retrovirus/RNA virus).

What is a provirus?

The DNA copy of an RNA virus genome that has been reverse transcribed and integrated into the host cell's genome (characteristic of RNA viruses like HTLV-1 and HCV).

What is an episome?

Circular viral DNA that persists in the infected cell nucleus without integrating into the host genome (characteristic of DNA viruses like HPV and EBV).

What is the difference between hyperplasia and neoplasia?

Hyperplasia = increased number of cells but all cells maintain normal regulatory control (does NOT lead to cancer on its own). Neoplasia = after dysplasia/metaplasia; rapid growth that results in tumour formation metastasis and acquisition of more mutations.

What is the correct order of progression from normal cell to cancer?

Normal → Hyperplasia → Dysplasia → Metaplasia → Neoplasia → Cancer (with metastasis).

How many mutations are typically required to cause cancer?

Multiple mutations: 3-20 total mutations are required. Recent research suggests 1-10 "driver" mutations are needed depending on cancer type.

Why is cancer more common in older people?

Carcinogenesis is a multistep process requiring accumulation of mutations over time. This takes years/decades so incidence rises sharply with age (1/3 of cancers in people aged 75+).

What is the approximate percentage of cancers that are carcinomas versus sarcomas?

Carcinomas = 85% of all cancers. Sarcomas = ~12% of all cancers.

What are the 5 factors used to stage cancer?

1) Site of primary tumour. 2) Size. 3) Local invasion extent. 4) Spread to regional lymph nodes. 5) Metastasis to distant organs.

Which arm of the immune system is most important for fighting cancer?

CD8+ cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are the main anti-tumour immune cells.

Why do immunosuppressed patients have higher rates of certain cancers?

Their immune system cannot eliminate virus-infected cells. Most increased cancers in immunosuppressed patients are virus-induced cancers (e.g. EBV-associated lymphomas HPV-associated cancers).

What is the "seed and soil" hypothesis of metastasis?

Cancer cells (seeds) need a receptive tissue microenvironment (soil) to successfully colonise and form macroscopic metastases. Not all tissues are equally permissive. [The seed and soil hypothesis means cancer cells will only grow where the environment is right for them – just like a seed needs the right soil to grow into a plant.]

What are the two "enabling characteristics" that allow cancer cells to acquire hallmarks? (Reading)

1) Genome instability and mutation – increases mutation rate so hallmarks can be acquired faster. 2) Tumor-promoting inflammation – supplies growth factors survival factors and matrix-modifying enzymes.

What are the two "emerging hallmarks" added in the 2011 Hallmarks of Cancer paper? (Reading)

1) Reprogramming energy metabolism (Warburg effect – aerobic glycolysis). 2) Evading immune destruction (immunoediting).

What is the Warburg effect? (Reading)

Cancer cells use aerobic glycolysis – they convert glucose to lactate even when oxygen is present. This is less efficient for ATP but allows diversion of glycolytic intermediates into biosynthetic pathways for macromolecules (nucleosides amino acids).

What are cancer stem cells (CSCs) and why are they clinically important? (Reading)

CSCs are a subpopulation of cancer cells that can self-renew and seed new tumours. They are often resistant to chemotherapy and radiotherapy which explains tumour relapse and dormancy after treatment.

What is the invasion-metastasis cascade? (Reading)

Six steps: 1) Local invasion. 2) Intravasation into blood/lymph vessels. 3) Transit through circulation. 4) Extravasation into distant tissue. 5) Micrometastasis formation. 6) Colonization (growth into macroscopic metastasis – the rate-limiting step).

Give an example of a direct oncogenic virus and explain why it is direct.

HPV – the virus is found inside cervical cancer cells (monoclonal form). Viral proteins E6 and E7 directly inactivate p53 and Rb tumour suppressors.

Give an example of an indirect oncogenic virus and explain why it is indirect.

HBV or HCV – the virus is NOT found in liver cancer cells. Instead they cause chronic inflammation and liver damage leading to continuous cell division and mutation accumulation.