Q.54 Arrange the following events responsible for colon cancer in the correct order in which they occur.
A. The benign adenoma progresses to a malignant adenoma.
B. A single mutated cell starts to proliferate abnormally, giving rise to a proliferative cell population.
C. The cancer cells invade the underlying connective tissue and penetrate the blood and lymphatic vessels,
thereby spreading throughout the body.
D. Additional mutations follow, leading to subsequent formation of an adenoma.
Choose the correct answer from the options given below:
1. B, D, A, C
2. B, D, C, A
3. C, A, D, B
4. B, A, D, C
Colon Cancer Progression: Correct Sequence of Events
Colon cancer develops through a stepwise process known as the adenoma-carcinoma sequence, starting from a single mutated cell and progressing to metastasis. The correct order of events is B, D, A, C, corresponding to option 1.
Correct Answer
Option 1: B, D, A, C
This sequence follows the classic adenoma-carcinoma model where a single APC gene mutation initiates abnormal proliferation (B). Additional mutations like KRAS or TP53 then form a benign adenoma (D). The adenoma advances to malignant carcinoma (A), and finally, cancer invades tissues and metastasizes via blood/lymphatics (C).
Option Breakdowns
Option 1: B → D → A → C (Correct)
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Begins with initial mutation and proliferation (B).
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Followed by adenoma formation (D), malignant progression (A), then invasion/metastasis (C).
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Matches histological progression from hyperproliferative epithelium to invasive adenocarcinoma.
Option 2: B → D → C → A (Incorrect)
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Places invasion/metastasis (C) before malignancy (A), which reverses the timeline.
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Metastasis requires prior malignant transformation; adenomas remain benign without invasion.
Option 3: C → A → D → B (Incorrect)
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Starts with metastasis (C), which is impossible as the final stage.
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Logical order is reversed; initial proliferation (B) must precede all others.
Option 4: B → A → D → C (Incorrect)
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Positions malignant adenoma (A) before additional mutations form adenoma (D).
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Adenoma develops first via mutations post-initial proliferation; malignancy follows later.
Progression Stages Table
| Stage | Event Description | Key Genetic Changes | Duration Estimate |
|---|---|---|---|
| Initiation (B) | Single mutated cell proliferates abnormally | APC mutation | Early phase |
| Adenoma Formation (D) | Benign adenoma develops | KRAS, additional hits | Years |
| Malignant Progression (A) | Benign to malignant adenoma | TP53, DCC loss | 5-10 years total |
| Metastasis (C) | Invasion into tissue, vessels; spread | Full transformation | Advanced stage |
This model, established by Vogelstein, underscores why screening detects early adenomas to prevent cancer.
