Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neoplasia > Molecular Basis of Cancer > Flashcards

Molecular Basis of Cancer Flashcards

2.4

1
Q

Proto-oncogenes

A

Oncogenes are mutated genes that promote autonomous cell proliferation in cancer.

Pro-onocogenes are normal genes, which are activated by “gain of function” mutation leading to cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Tumor supressor

A

Are normal genes that slow down cell division or tell cell to die at the right time. (apoptosis)

Tumor suppressor are inactivated by ‘loss of function’ mutations which lead to cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Categories of onocogenes

A
  1. Growth factor - PDGFB
  2. Growth Factor receptor- ERBB1 and 2
  3. Signal transducer - RAS gene family
  4. Nuclear regulator - MYC
  5. Cell cycle regulator- Cyclins and CDK
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

The most frequently mutated oncogenic pathway in humans

A

Receptor Tyrosine kinase pathway
- Growth factor
-RAS
-GAP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Oncoproteins that are activated by mutations in cancer

A
  1. Growth Factor
  2. RAS - 90% of the cancer the RAS is mutated. When mutated they do not have GTPhase activity inside the RAS and GAP cannot do his function.
  3. PI3K
  4. MYC
  5. D-cyclins

When MYC and D-Cyclins are mutated the cell will continue to divide and multiple the cell cancers.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Tumor suppressors proteins

A
  1. GAPs are the one that will inactive the GTP bind to RAS by hydrolysis.
  2. PTEN is going to inactive PI3K and prevent from activating AKT signaling

GAPs break RAS signaling and PTEN breaks AKT/PKB signaling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Oncogene activation mechanism

A

Proto-oncogenes are activated by 3 mechanism

  1. Point mutation
  2. Gene amplification
  3. Chromosomal translocation
    a. Overexpression- a piece of another one binds to promotor and promotes his overexpression. IG gene enchances MYC activity.
     b. Chimeric protein - Translocation happen but they are fuse together to create a Hybrid. ABL-BCR hybrid will increase Tyrosine kinase activity.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Chronic Myeloid Leukemia

A

Example of Chimeric protein.
t (9;22)

Fusion of ABL oncogene and BCR locus (ABL-BCR hybrid gene) will increase the activity of Tyrosine kinase to activate the growth factors for signaling pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Burkitt Lymphoma

A

Example of Overexpression

Is when IG gene will enhance the activity of MYC oncogene. They do not fusion to create an hybrid gene.

Chromosome 14 (IGH) and 8 (c-MYC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Diffuse Large B- cell lymphoma translocation

A

Chromosome 14 ( IGH) and Chromosome 3 (BCL-6)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Burkitt lymphoma translocation

A

Chromosome 14 (IGH) and Chromosome 8 (c-MYC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Mantle cell lymphoma translocation

A

Chromosome 14 (IGH) and Chromosome 11 (CCND1/Cyclin D1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Follicular Lymphoma translocation

A

Chromosome 14 (IGH) and Chromosome 18 (BCL-2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

c-SIS/ PDFB

A

Platelet derived growth factor

overexpression causes Astrocytoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

ALK; ERBB1 (EGFR)

A

Receptor tyrosine kinase

A point mutation causes Lung adenocarcinoma (NSCLC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

ERBB2 (HER2/neu)

A

Receptor tyrosine kinase

Amplification causes Breast Carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

RET

A

Receptor tyrosine kinase

point mutation causes
- Pheochromocytoma- tumor that grows from cells called chromaffin cells
- Medullary thyroid carcinoma
-MEN2A and 2B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

c-KIT

A

Cytokine receptor (CD117)

Point mutation causes Gastrointestinal Stromal Tumors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

KRAS

A

GTP binding Protein

Point mutation causes
-Colon tumor
-Lung tumor
-Pancreatic tumor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

NRAS

A

GTP binding protein

Point mutation causes Hemotologic malignancies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

HRAS

A

GTP binging protein

point mutation causes Bladder and Kidney cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

ABL

A

Non receptor tyrosine kinase

t (9;22)- ABL-BCR
Chronic myeloid leukemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

BRAF

A

Serine/ threonine kinase

point mutation Melanoma, hairy cell leukemia

24
Q

JAK2

A

non receptor tyrosine kinase

point mutation Myeloproliferative disorder

25
Q

C-MYC

A

Transcription factor

t( 8;14) involving IGH
Burkitt lymphoma

26
Q

N-MYC

A

Transcription factor

Amplification- Neuroblastoma

27
Q

L-MYC

A

transcription factor

amplificacion- lung carcinoma (smalll cell)

28
Q

CCND1

A

Cyclin D1

t(11;14) involving IgH
Mantle cell lymphoma

29
Q

CDK4

A

Cyclin- dependent kinase

amplification- Melanoma

30
Q

Two mutation affecting the cell cycle regulator

A
  1. Gain of function mutation in Cyclin D and CDK4.
    They phosphorylates the RB so that he can free E2F and promote the cycle to enter to S-phase.
  2. Loss of function mutation in the gene that inhibit G1/S.
    -CDK inhibitor
    - RB
    -TP53

CDK inhibitors (p16 and p21) are supposed to stop the CDK from working.

RB dephosphorylated is blocking E2F and transcription is blocked.

TP53 makes a protein that is found inside the nucleus of cells and plays a key role in controlling cell division and cell death. Is important regulator of GS1/M

31
Q

The most common neoplasm related to RB mutation

A

Retinoblastoma and Osteosarcoma

Retinoblastoma is involve in a two mutation hit. Involving both alleles of Rb

32
Q

What are the two activators for p53 following DNA damage?

A

ATM and ATR

33
Q

What happens in DNA damage?

A

DNA damage promotes MDM2 degradation and p53 stabilization

34
Q

TP53

A

Regulates the cell cycle

Most frequently mutated gene in human cancer.

Most of mutations a acquired in somatic cells nor inherited.

Exception- Li Fraumeni syndrome
They have a broad of variety/spetrum of multiple cancer on early onset.

35
Q

Li-Fraumeni syndrome

A

Individuals inherited one mutated p53 allele.

They have a broad spectrum of cancer. Sarcomas, brain tumor, leukemias, carcinomas.

36
Q

APC: gatekeeper of colonic neoplasia

A

The APC is gonna downregulate the growth promoting signaling pathway by destroying beta catenin. this inhibits proliferation.

If APC is not working it cannot destroyed the beta-catenin and the cancer cell will proliferate.

Loss of function mutation in APC is responsible for Familial adenomatous polyposis (FAP). Condition where adenomatous polyps arise in the colorectal epithelium

37
Q

Ways to lead to proliferation of cancer cell by APC gatekeeper pathway

A
  1. No E-cadherin
  2. over-expression of Beta catenin
  3. APC nor functioning
38
Q

Familial adenomatous polyposis (FAP)

A

Loss of function mutation in APC is responsible for Familial adenomatous polyposis (FAP). Condition where adenomatous polyps arise in the colorectal epithelium

39
Q

Germline Loss of function of E-cadherin gene ( CDH1)

A

Familial gastric carcinoma and infiltrating lobular carcinoma (ILC) of the breast cancer.

The beta catenin is bind do E-cadherin. NO binding will cause Beta catenin to be free and common cause for breast cancer.

40
Q

TGF- beta

A

TGF- beta is a potent inhibitor of cell proliferation by turning ON anti-proliferative gene (CDK inhibitors) and turning OFF the genes that drive the cell growth (MYC, Cyclins, CDKs).

The lost of TGF-Beta is critical role for most pancreatic cancers.

41
Q

Von Hippel- Lindau Tumor Suppressor (VLH)

A

VLH is involved in the ubiquitination and degradation of HIF (Hypoxia inducible factor)

Normoxia- Hydroxylation in the presence of O2 HIF is detached from VHL and HIF is degraded.

Pseudohypoxia - “Von hippel lindau syndrome” the cell is not hypoxic but the VLH is not functioning so they think the cell is hypoxic and there is no degradation of HIF.

‘Loss of function’ of VLH
the Von Hippel Lindau syndrome predisposes to
- Hemangioblastomas
- renal cell carcinomas
- pheochromocytoma

42
Q

Loss RB1; Ch13

A

Inhibitor of G1/S transition (E2F binding)

Familial retinoblastoma
osteosarcoma

43
Q

Loss TP53; Ch 17q

A

Regulates cell cycle and apoptosis

Li-Fraumeni syndrom- family history of differents cancer at young on set.

44
Q

Loss CDK2A- p16/INK4a

A

Inhibitor of cyclin D/CDK4,6 (block the cell progression from G1 to S)

Familial melanoma
familial pancreatic carcinoma

45
Q

Loss APC, Ch5q

A

Regulates levels of Beta-catenin protein

Familial adenomatous polys and carcinoma

46
Q

LOSS BRCA1, 17q and 2, 13q

A

Repair DNA double- standed breaks

Familial breast and ovarian cancer

THE FAMILY HAVE TO HAVE A HISTORY OF BREAST CANCER AND OVARIAN

47
Q

LOSS NF1 (GAP), 17p- Neurofibromin

A

Inhibitor of RAS/MAPK signaling

Neurofibromatosis type 1

48
Q

LOSS NF2, Ch22- Merlin

A

Contact dependent growth inhibition

Neurofibromatosis Type 2

49
Q

VHL; Ch 3

A

Inhibitor of hypoxic induced transcription factor (HIF)

Von Hippel Lindau syndrome
Cerebellar hemangioblastoma
Renal cell carcinoma

50
Q

PTEN

A

Inhibitor of PI3K/AKT signaling

Prostate cancer
Breast cancer
Endometrial cancer

51
Q

WT1, Ch11

A

Familial Wilms tumor (neuroblastoma)

52
Q

MSH2 and 6; MLH1

A

DNA mismatch repair

Hereditary non-polyposis colorectal cancer

53
Q

TSC1 (9)- HAMARTIN
TSC2 (16)- TUBERIN

A

inhibitor of mTOR signaling

Tuberous sclerosis

54
Q

MEN 1 - Menin

A

Inhibit Jun D- mediated transcription factor

Multiple endocrine neoplasia type 1
(Pituitary, parathyroid, pancreatic tumor)

55
Q

SMAD 2 and 4

A

Antiproliferative responses to TGF-B

Juvenile polyposis, Pancreatic cancer

Neoplasia (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions