30 Clinical Examples of Cancer Drivers Flashcards

(44 cards)

1
Q

Name 2 oncogenes and the FORM of leukemia that they drive

A

MYC - Burkitt’s lymphoma (AGGRESSIVE)

Bcl2 - Follicular lymphoma (indolent)

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2
Q

What are the PRECURSORS of oncogenes?

What is their function?

A

PROTO-oncogenes drive growth + differentiation

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3
Q

Upon mutation of proto-oncogenes to form oncogenes, what cellular changes can oncogenes DRIVE?

A

HyperACTIVE protein

More EXPRESSION of normal protein

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4
Q

Name 5 genetic changes that can cause conversion of a proto- to an ONCOGENE

A
  1. CODING seq mutation
  2. Gene AMPLFICATION
  3. Rearrangements (FUSION protein)
  4. Rearrangements (near strong PROMOTER)
  5. KO neg feedback
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5
Q

Effects of:

  1. CODING seq mutation
  2. Gene AMPLFICATION
  3. Rearrangements (FUSION protein)
  4. Rearrangements (near strong PROMOTER)
  5. KO neg feedback
A
  1. HYPERactive protein (normal amount)
  2. EXCESS expression (normal protein)
  3. HYPERactive protein (normal amount)
  4. EXCESS expression (normal protein)
  5. EXCESS expression (normal protein)
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6
Q

Secondary immune organs are the SITES of _____

A

ANTIGEN-driven replication + maturation

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7
Q

Where does B-cell production begin?

What happens?

A

Haematopoietic SCs develop into NAIVE B-cells

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8
Q

Define NAIVE B-cells

A

BCR has no exposure to antigens yet

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9
Q

Where do naive B-cells go for maturation?

What happens?

A

Lymph nodes

= BCR on naive cells EXPOSED to antigens in follicles

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10
Q

The exposure of BCRs to antigens, and subsequent maturation is called

A

Transformation

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11
Q

Describe the morphology of LNs before vs after antigen-exposure

A

BEFORE antigen-exposure = SMALL primary follicles

AFTER antigen-exposure = LARGE secondary follicles

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12
Q

“Transformation” is AKA

A

Germical Centre reaction

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13
Q

At the germinal centre, what are the 2 “populations” of cells, and how do they differ?

A

LIGHT zone = proliferating MATURE B-cells

DARK zone = DYING weak-binding cells

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14
Q

What events occur in the BONE MARROW and LNs to promote Ig gene-rearrangements?

A

Bone marrow
= VDJ recombination to create UNIQUE BCRs

Lymph nodes (upon antigen-exposure)
= POINT MUT in V/D/J genes
= Different CLASSES of Ig formed

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15
Q

What is a “dangerous” aspect of Ig gene-rearrangements

A

Forms many DSBs and REPAIR of these

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16
Q

What kind of DSB-repair ERROR occurs?

A

Reciprocal Balanced Transition (no DNA lost)

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17
Q

What kind of recombination specifically occurs in Burkitts and Follicular lymphoma?

A

Burkitts = recombination of IGH promoter + MYC
= t(8;14)
Follicular = recombination of IGH promoter + Bcl2
= t(14;18)

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18
Q

What chr is the IGH promoter on?

19
Q

How are such FUSIONS detected?

20
Q

Effects of MYC as an oncogene?

What hallmarks does it control?

A

Controls all cancer hallmarks except 1 (MILESSEGII)
*Metastasis - dec cell adhesion
*Insensitive to anti-growth - immortalised cells have inc telomerase activity
*Limitless growth potential
*
*Self-sufficient growth - glycolysis+glutaminolysis to support BIOMASS synthesis
*Sustained angiogenesis

  • Energetics dysregulation
  • Genome instability
  • Immune evasion
  • Inflammation
21
Q

What hallmark does MYC NOT control?

A

APOPTOSIS is maintained normally

22
Q

Describe the HISTOLOGY of Burkitt’s lymphoma cells

A
  • many LARGE BLASTS
  • dark BLUE cytoplasm
  • OPEN chromatin
  • can REPLACE LN structure
  • Smear + DYING celsl common
23
Q

What immune cell type is COMMON in Burkitt’s ?

Why?

A

Macrophages - phagocytic for apoptotic cells

24
Q

What molecular MARKER is 100% expressed in Burkitt’s cells? What does it suggest?

A

Ki67 = proliferation cycling marker

25
Burkitt's lymphoma slides are often said to have a ________ appearance Why?
"Starry Sky" - spaces due to ongoing APOPTOSIS
26
Describe the aggressiveness of Burkitts progression?
Rapidly GROWING abdominal tumors | Rapid SPREAD to blood + bone marrow
27
What is an ASSOCIATED syndrome of Burkitts?
TOXINS (urate) from spontaneous cell death (tumor lysis syndrome) can cause RENAL FAILURE
28
Due to the HUGE # of blasts, what is often clinically required for Burkitts patients? What is their STATUS?
Haematological EMERGENCY | = requires URGENT chemoTx
29
"Advantage" of Burkitt's as a leukemia?
Responds WELL to treatment | highly CURABLE to immediate chemoTx due to intact APOPTOSIS
30
What is Bcl-2's normal function
ANTI-apoptotic protein | = inhibits Bak/bax to prevent apoptotsis
31
Describe CLINICAL features of follicular lymphoma
* SLOW proliferation * SLOW progressive spread to other Lns * Usually ISOLATED lymphadenopathy (often accidental finding)
32
"DANGER" of follicular lymphoma as a leukemia?
RESISTANT to apoptosis = cells just don't die and accumulate = NOT CURABLE
33
Morphology of follicular lymphoma cells
* Small, mature lymphocutes * Nuclear cleaving common * Bcl2 OVEREXP
34
The PROGNOSIS of follicular lymphoma is determined using...
STAGING (depends on BULK of tumor)
35
List the stages of follicular lymphoma and define
Stage I - isolated tumor Stage 2- dissemination to secondary sites Stage 3-4 - dissemination
36
do cellular properties change during dissemination?
NO CHANGE | remains the SAME in mets
37
PROGNOSIS of follicular lymphoma depends on ___ of tumor
BULK (size)
38
name 3 infiltrative complications of follicular lymphoma
Bone marrow - impair haematopoiesis = LOW peripheral blood counts COMPRESSION of structures - SC, ureters EFFUSIONS - pleural, pericardial, peritoneal
39
Therapies for follicular lymphoma throughout progression?
Primary tumor = excision, radioTx | Advanced = chemoTx, anti-CD20 antibodies
40
The process of a leukemia becoming ACUTE is termed
Transformation
41
What EVENT does transformation require?
SECONDARY genetic HITS = "Double-hit" lymphoma
42
Examples of secondary genetic hits that can occur to transform follicular lymphoma into ACUTE
* KO TP53 | * activating MYC
43
HIGHER grade lymphomas will show what characteristic in BIOPSIES?
more LARGE cells
44
Symptoms of TRANSFORMED acute follicular lymphomas
* LNs enlarge RAPIDLY | * SYSTEMIC symptoms (fever, night sweats, weight loss)