Question 1

Why does a single mutation not cause cancer immediately?

Accepted Answer

A single mutation is insufficient to transform a healthy cell into a cancerous cell. Cancer development requires at least five to six independent and rare genetic alterations occurring in succession over time. This multi-step process, explained by multi-hit theory, allows cells to progressively gain oncogenicity through accumulation of mutations in different cancer-critical genes.

Question 2

What is the difference between somatic and inherited cancer mutations?

Accepted Answer

Somatic mutations develop in body cells during an organism's lifetime and are not inherited, accounting for the majority of the over 570 frequently mutated cancer genes. Inherited mutations, by contrast, are passed from parents to offspring. Most cancers arise from somatic mutations acquired in individual cells rather than from germline mutations present at birth.

Question 3

How does the multi-hit theory explain cancer progression?

Accepted Answer

Multi-hit theory describes cancer as a sequential process where a single mutant cell acquires additional mutations in different genes over time. Each mutation provides a selective advantage—such as faster division, increased mutation rates, or escape from apoptosis—allowing the cell line to accumulate more mutations and eventually become malignant.

Question 4

What types of genetic changes can lead to cancer development?

Accepted Answer

Cancer-causing mutations include point mutations, indels, large-scale chromosomal deletions, and translocations. For example, aristolochic acid exposure causes A to T base substitutions, while breast cancer BRCA1 and BRCA2 mutations involve indels and deletions. CML features the Philadelphia chromosome, a translocation between chromosomes 9 and 22.

Question 5

How does cancer evolution relate to Darwinian principles?

Accepted Answer

Cancer cell evolution mirrors Darwinian evolution, where each cancer-critical mutation is naturally selected and fixed in the population. Cells with advantageous mutations outcompete neighboring cells, establishing clonal populations. This evolutionary process explains why cancer development typically requires substantial time and multiple independent mutations.

Question 6

Why does cancer incidence increase with age?

Accepted Answer

Cancer typically requires numerous independent, rare genetic mutations and epigenetic changes accumulating in a single cell's lineage over time. This extended timeline explains the increased cancer incidence with age. For example, median diagnosis ages are 61 years for breast cancer, 68 years for colorectal cancer, and 70 years for lung cancer.

Question 7

What are examples of cancer-critical genes frequently mutated in colon carcinoma?

Accepted Answer

Frequently mutated cancer-critical genes in colon carcinoma include APC, c-Myc, K-Ras, and p53. These genes regulate cell cycle control, metabolism, and apoptosis. Mutations in these genes allow cells to escape normal growth regulation and accumulate additional mutations, driving tumor formation and progression.

Os cânceres se originam de mutações somáticas em uma única célula

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