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Term III: Pathology > Neoplasia IV-VI > Flashcards

Neoplasia IV-VI Flashcards

1
Q

What is the most common type of mutation in inherited cancer syndromes?

A

Point mutation in a single allele of a tumor suppressor gene

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2
Q

What are three autosomal dominant inherited cancer syndromes and what is their associated mutation?

A
  1. Familial adenomatous polyposis - APC gene
  2. Li-Fraumeni syndrome - p53 gene
  3. MEN-1 and MEN-2 - transcription factors
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3
Q

What type of mutation contributes to development of the malignant phenotype?

A

Driver mutations

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4
Q

What type of mutation leads to genomic instability and greatly increases the frequency of mutations?

A

Passenger mutations

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5
Q

What type of mutation maintains genomic integrity and appears to be a common early step on the road to malignancy?

A

Loss-of-function mutations

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6
Q

What are two epigenetic modifications that can lead to cancers?

A
  1. DNA methylation

2. Modifications of histones

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7
Q

Name the 8 key changes in malignancy.

A
  1. Self sufficiency in growth signals
  2. Insensitivity to growth-inhibitory signals
  3. Evasion of apoptosis
  4. Limitless replicative potential
  5. Sustained angiogenesis
  6. Ability to invade or metastasize
  7. Defects in DNA repair
  8. Altered cellular metabolism
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8
Q

What cytokine are many tumor cells resistant to?

A

TGF-beta

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9
Q

What is the name of genes that promote autonomous cell growth in cancer cells?

A

Oncogenes

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10
Q

What is the name of genes that promote normal cell growth and development?

A

Proto-oncogenes

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11
Q

What are the three ways oncogenes can be activated?

A
  1. Change in gene structure
  2. Gene amplification
  3. Change in gene regulation
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12
Q

What are the three variants of the RAS oncogene in humans?

A

HRAS, KRAS, NRAS

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13
Q

What is the single most common abnormality of proto-oncogenes in human tumors?

A

Point mutation in RAS family of genes

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14
Q

What gene is a serine/threonine protein kinase that is upstream of the MAPK family of serine/threonine protein kinases?

A

BRAF

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15
Q

What gene activates a cascade of serine/threonine kinases including AKT?

A

PI3K

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16
Q

What cancer involves a BCR-ABL tyrosine kinase as a result of a chromosomal translocation? What chromosomes does it involve?

A

Chronic myelogenous leukemia

9 –> 22

17
Q

Name a class of nonreceptor tyrosine kinases that can be activated by point mutations?

A

JAK-STAT

18
Q

Name the transcription factor that is most commonly involved in human tumors.

A

MYC

19
Q

What enzyme can MYC upregulate that allows it to reprogram somatic cells into pluripotent stem cells?

A

Telomerase

20
Q

Which cyclin is overexpressed in breast, esophagus, liver, and some lymphomas?

A

Cyclin D

21
Q

Amplification of what CDK gene occurs in melanomas, sarcomas, glioblastomas?

A

CDK4

22
Q

What are some examples of tumor suppressor genes?

A
  • Rb (retinoblastoma)
  • p53
  • BRCA 1&2
  • APC
23
Q

What is the name of the syndrome that involves inheritance of a mutated copy of p53?

A

Li-Fraumeni syndrome

24
Q

What are the three interlocking mechanisms p53 uses to thwart neoplastic transformation?

A
  • Activation of temporary cycle arrest (quiescence)
  • Induction of permanent cell cycle arrest (senescence)
  • Triggering of programmed cell death (apoptosis)
25
Q

What family of proteins stimulates degradation of p53?

A

MDM2

26
Q

What are the two related protein kinases that are key initiators of p53 activation?

A

Ataxia telangiectasia and Rad3

27
Q

What part of cell cycle does transient p53 block the progression of?

A

G1 to S (arrest occurs late in G1)

28
Q

What pro-apoptotic genes does p53 direct?

A

BAX and PUMA

29
Q

Give 2 examples of tumors that have wild type p53 alleles?

A

Testicular tumors and childhood acute lymphoblastic leukemias

30
Q

Give 2 examples of tumors that have mutated p53 alleles?

A

Lung and colorectal cancers

31
Q

What is the class of tumor suppressors whose main function is to down-regulate growth promoting signals? (Hint: its loss often leads to colorectal cancers)

A

APC - adenomatous polyposis coli genes

32
Q

What are the two phases of the metastatic cascade?

A

1 - invasion of ECM

2 - vascular dissemination, homing of tumor cells, colonization

33
Q

What receptors do tumors upregulate to attach to matrix components?

A

Laminin and fibronectin

34
Q

What are the 4 theories of metastatic development?

A
  1. Metastatic variants
  2. Metastatic signature
  3. Metastatic variants + signature
  4. Metastatic signature + variants + stromal response
35
Q

Define “grade” of tumors.

A

HISTOLOGIC - Degree of differentiation (well-differentiated, poorly differentiated, etc.)

36
Q

Define “stage” of tumors.

Give an example of staging for lymphomas.

A

CLINICAL - size of tumor and extent of spread

Ex: lymphomas
I - localized, IV - extranodal metastasis

37
Q

What is the TNM system?

A

T - size of tumor
N - # nodes involved
M - distant metastasis

Term III: Pathology (12 decks)

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