Neoplasia (7) - Self-sufficiency in Growth Signaling

Question 1

Germline mutations

Answer 1

Heritable!

- DNA is mutated from the beginning of development

Question 2

Germline mutations are seen in what type of cancer syndromes?

Answer 2

Familial

Question 3

Somatic mutations

Answer 3

NON-heritable; Acquired over lifetime

Question 4

With Proto-oncogenes, how does cancer arise?

Answer 4

A mutation = Gain of function

Question 5

With Tumor-suppressor genes, how does cancer arise?

Answer 5

2 mutations = Loss of function

Question 6

With Apoptosis regulating genes, how does cancer arise?

Answer 6

Suppress Apoptosis

Question 7

With DNA repair genes, how does cancer arise?

Answer 7

Loss of function

Question 8

Driver mutations

Answer 8

CAUSE cell growth

Question 9

Passenger mutations

Answer 9

Do not directly cause cancer but are along for the ride with driver mutations

Question 10

Normal gene that when mutated, becomes an oncogene

Answer 10

Proto-oncogene

Question 11

Mutated gene that results in excessive cell growth

Answer 11

Oncogene

Question 12

Amplification of Growth receptors on the cell membrane result in?

Answer 12

More receptors create more opportunities for growth factors to stimulate cell proliferation and growth!

Question 13

What is an example of an amplification of a growth receptor that results in cancer?

Answer 13

Her-2/neu results in breast cancer

Question 14

How do you treat breast cancer that was caused by Her-2/neu growth receptor amplification?

Answer 14

Herceptin - antibodies to the Her-2/neu receptors on the cell inhibit growth factors from binding and activating the cell to grow

Question 15

What does RAS normally do?

Answer 15

Activates all downstream cell events for growth and proliferation after a growth hormone binds the growth receptor on the cell

Question 16

When RAS is active, what is it bound to?

Answer 16

GTP

Question 17

When RAS is inactive, what is it bound to?

Answer 17

GDP

Question 18

Point mutations in RAS will cause?

Answer 18

RAS will be constitutively active and stuck to GTP; even in no presence of a growth factor!!

Question 19

With what cancers are point mutations in RAS that cause it to be stuck to GTP and always active seen?

Answer 19

Pancreas, lung and colon cancers

Question 20

Normal job of PTEN?

Answer 20

INHIBITS p13k pathway that RAS-GTP activates

– STOPS the cell signaling

Question 21

When PTEN is inactive, what occurs?

Answer 21

RAS-GTP activates the P13K pathway and cell signaling/growth occurs!

Question 22

A loss of function mutation of PTEN is seen with what cancer?

Answer 22

Endometrial carcinomas

Question 23

Endometrial cancers have a loss of function mutation in PTEN. Describe what happens.

Answer 23

RAS-GTP is active and activates the P13K pathway. With NO PTEN to STOP this p13k pathway, cell growth and proliferation signals are passed on!

Question 24

With Chronic Myeloid Leukemia, what chromosomal abnormality is present?

Answer 24

Translocation

Question 25

With Chronic Myeloid Leukemia, what genes are translocated to be together?

Answer 25

BCR-ABL

Question 26

What does the BCR-ABL translocation activate and what does that ultimately result in?

Answer 26

Activates Tyrosine Kinases that stimulate growth

= Chronic Myeloid Leukemia

Question 27

What is oncogene addiction?

Answer 27

Tumor genesis is DEPENDENT on a particular protein

Question 28

What is an example of oncogene addiction?

Answer 28

BCR-ABL with chronic myeloid leukemia

Question 29

How can you treat chronic myeloid leukemia?

Answer 29

Tyrosine Kinase INHIBITORS

– Blocks the Tyrosine Kinases that BCR-ABL is activating for cell growth

Question 30

What is MYC?

Answer 30

Master transcriptional regulator

Question 31

If MYC is active, what is increased?

Answer 31

MYC is a transcription agent

= INCREASED Protein synthesis and thus cell growth

Question 32

Amplification of MYC is seen with what cancer?

Answer 32

Neuroblastoma

Question 33

Neuroblastoma often affects what population?

Answer 33

Children

Question 34

Neuroblastoma has an amplification of?

Answer 34

MYC

Question 35

If Cyclin D1 is active, what will result?

Answer 35

Cell cycle is ACTIVE

Question 36

If Cyclin D1 is inactive, what will result?

Answer 36

NO CELL CYCLE OCCURRING

Question 37

With what cancer is Cyclin D1 always active and stimulating the cell cycle to occur?

Answer 37

Mantle cell lymphoma

Question 38

Normally, what is the job of P16?

Answer 38

INHIBITS Cyclin D1 and thus INHIBITS the cell cycle from occurring

Question 39

P16 inhibits ____

Answer 39

Cyclin D1

- And thus the cell cycle

Question 40

Germline loss of P16 creates what type of cancer?

Answer 40

FAMILIAL Melanomas - inherited

Question 41

If P16 loses function, what results?

Answer 41

It canNOT inhibit Cyclin D1, so the cell cycle will progress and cell growth and proliferation will occur