Multistep models of colorectal tumorigenesis Flashcards

Colon and other gastrointestinal cancers, chapter 48, page 653

1
Q

The …………-……….. sequence best models the genetic basis of CRC?

A

Adenoma-carcinoma sequence

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2
Q

CRCs invariably arise within benign precursor polyps. List the four features these polyps show.

A
  1. Epithelial overgrowth
  2. Dysplasia
  3. Abnormal differentiation
  4. Sometimes, foci of tissue invasion
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3
Q

What type of polyps are the most significant risk for development of CRC?

A

Pedunculated polyps >1cm

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4
Q

A pedunculated polyp >1cm harbours a …..% risk of progressing to CRC over …. years. Endoscopic removal of these adenomas reduces CRC incidence and mortality.

A

15% over ten years.

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5
Q

The prevalence of polyps in the US is estimated to be ….% at age 70. This dwarfs the 6% lifetime risk of developing CRC because few adenomas progress to invasive cancer, and the successive abberations that promote invasion take … to …. decades to accumulate.

A

50% at age 70.

1-3 decades to accumulate

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6
Q

What are the two types of serrated CRC precursor lesion forms?

A
  • Serrated adenomas with cytologic dysplasia

- Sessile serrated adenomas without cytologic dysplasia

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7
Q

A serrated adenoma with cytologic dysplasia may evolve into what type of CRC with what underlying genetic abnormality?

A

Common CRCs with chromosomal instability and KRAS mutation

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8
Q

A sessile serrated adenoma without cytologic dysplasia may evolve into what type of CRC with what underlying genetic abnormality?

A

CRCs with microsatellite instability (MSI-hi), BRAF mutation, and abundant CpG island methylation.

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9
Q

Approximately ….% of CRCs arise within serrated lesions, retain a serrated epithelium with characteristic ……… ……………., and carry a relatively ……. prognosis.

A

8%, nuclear morphology, poor prognosis.

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10
Q

Cancer progression has both genetic and epigenetic underpinnings. What is meant by the terms genetic and epigenetic in this context?

A
Genetic = somatic mutations
Epigenetic = unrelated to altered DNA sequence
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11
Q

Alterations in several classes of genes drive tumours. List three.

A
  1. Oncogenes
  2. Tumour supressor genes (including those that assist with repair of damaged DNA)
  3. Epigenetic modifiers - those that help control other genes.
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12
Q

Selected mutations appear at high frequencies in different tumour types and stages, allowing for the assignment of typical sequences, although mutational …… can vary and most tumours do not carry ….. ………… .

A

Selected mutations appear at high frequencies in different tumour types and stages, allowing for the assignment of typical sequences, although mutational ORDER can vary and most tumours do not carry EVERY ALTERATION .

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13
Q

Few specific mutations correlate strongly with particular ………. …….., or …….. …….. . Most affect multiple cellular functions

A

Few specific mutations correlate strongly with particular histologic features, or patient survival . Most affect multiple cellular functions.

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14
Q

Particular …………… do define CRC subtypes, and response to certain therapies

A

genotypes

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15
Q

Where do MSI-hi tumours tend to arise? Are the associated with good or poor prognosis?

A

The ascending colon

Good prognosis

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16
Q

In stage II MSI tumours, which adjuvant treatment provides little benefit?

A

5-fluorouracil

17
Q

Which mutations account for approximately half of all cases?

A

KRAS and BRAF

18
Q

How do KRAS and BRAF mutations affect response to adjuvant therapy?

A

KRAS and BRAF limit response to epidermal growth factor receptor antibodies (EGFR antibodies). They are contraindications for this treatment.