deck_4851667

Question 1

Which cells skip the G0 phase entirely?

Answer 1

bone marrow cells (rapidly divide)

Question 2

When does DNA replication occur in cell division?

Answer 2

S phase (interphase includes G1, S, and G2)

Question 3

What is the difference between G1 and G2 phases?

Answer 3

In G1, the cell synthesizes DNA and proteins and increase cytosokeletal and chromatin are made (chromatin is long and slender), while in G2 RNA and proteins are synthesized and proof-reading occurs. Cell repair for DNA from S phase occurs here.

Question 4

What follows interphase (specifically G2)?

Answer 4

Mitosis (prophase, metaphase, anaphase, and telophase)

Question 5

Where is the cell-cycle controlled?

Answer 5

between G1 and S before DNA replication and between G2 and mitosis

Question 6

What are cyclin-dependent kinases (CDKs)?

Answer 6

kinases add phosphate groups to activate or inactive them (control cell cycle)always present in a cell but default form is inactive- activated by cyclins

Question 7

What are specific cyclins?

Answer 7

cyclin made at specific times to activate CDKs by binding to them. NOT always available

Question 8

Which cyclins are made before entering S from G1? Which CDKs do they bind to?

Answer 8

cyclins D and E. These bind to CDK2 (cyclin E) and CDK4 (bound to cyclin D).

Question 9

What does CDK4 (complexed with cyclin D) do?

Answer 9

phosphorylates the RB protein, keeping it from inhibiting the S phase

Question 10

What cyclins are made in the S phase? What CDK does it complex with?

Answer 10

cyclin A (complexes with CDK2 to activate it)

Question 11

What does CDK2 bound to cyclin A do?

Answer 11

activates DNA replication during S phase

Question 12

What cyclins are made in the G2 phase? Which CDK does it complex with?

Answer 12

cyclin B (complexes with CDK1) to activate mitosis

Question 13

What are cancer genes?

Answer 13

Genes that, in their normal form, are responsible for critical aspects of human development, control of the cell cycle, etc. but have caused malignancy when they are out of control aka Genes that, when mutated, enable dysregulated cell growth

Question 14

T or F. Loss of heterozygosity is not relevant to oncogenes

Answer 14

T. It only has to do with tumor suppressor genes

Question 15

What are oncogenes?

Answer 15

growth promoting genes. Carcinogenic mutation of these gains often manifest as a gain of function, in which growth in unregulated In contrast, cancer causing mutations in tumor suppressor genes are loss of function

Question 16

At the CELLULAR level, what does it mean that oncogenes have a dominant cellular phenotype, while TSGs have a recessive cellular phenotype?

Answer 16

This means that mutation of one allele of an oncogene will result in gain of function, while it will take mutation of both TSGs to result in loss of function

Question 17

What are the main ways through which an oncogene can mutate to a gain of function cancerous gene?

Answer 17

1) mutation in coding sequence- hyperactive protein made in normal amounts (Ras)2) gene amplification- normal protein overproduced (Myc, Cyclin D, Erb-B1)3) balanced translocation- nearby regulatory DNA sequence causes normal protein to be overproduced (Myc, Cyclin D, Bcl-2, Src, Raf) or fusion to actively transcribed gene greatly overproduces fusion proteins; or fusion protein is hyperactive (Abl)

Question 18

How does point mutation cause gain of function of the RAS gene (which is activated in many tumors)?

Answer 18

• GTP hydrolysis required for normal inactivation of RAS.• Somatically acquired mutations in the RAS gene that interfere with the ability of the protein to bind/hydrolyze GTP allow RAS protein to remain constitutively active

Question 19

What is the basis of gene amplification?

Answer 19

Tumor cells with hundreds of copies of a proto-oncogene, conferring selective growth advantage

Question 20

What are the two types of microscopic gene amplification?

Answer 20

– HSR (Homogeneously Staining Regions)• visible in chromosomes as an extra, non-banded region– DM (Double Minutes)• extrachromosomal gene able to replicate and segregate randomly, circular with no centromere or telomeres • Segregate randomly at cell division (unstable)

Question 21

Cancer As a Multi-Step Process

Answer 21

• Malignant transformation involves multiple acquired (somatic) mutations• Tumors evolve and progress by clonal evolution• Advanced malignancies have a large burden of genetic abnormalities as well as genomic instability.– Multiple driver mutations (“cancer genes”) – Many passenger mutations

Question 22

What are constitutional mutations?

Answer 22

present in all cells of the body (germline & somatic). Includes (and doesn’t differentiate between) inherited mutations & new mutations.

Question 23

What are acquired mutations?

Answer 23

mutation that arises in a somatic cell. It will be passed ONLY to its own daughter cells (clonal expansion). It will NOT be passed to offspring.

Question 24

What is an inherited mutation?

Answer 24

genetic variant inherited from a parent and present in gametes and in all somatic cells of the body.

Question 25

Oncogenes Do Their Damage via Somatic (Acquired) Mutations

Answer 25

– Overwhelmingly, tumorigenic changes in oncogenes arise as somatic mutations.– Although almost every tumor will have abnormal function of one or more oncogenes, the same loci are homozygous normal in somatic tissue.– Very few hereditary cancers are caused by oncogenes• Exception: RET proto-oncogene and MEN2 [multiple endocrine neoplasia type 2]Tumor suppressor genes account for the majority of hereditary cancers

Question 26

What is BRAF V600/Venumafenib?

Answer 26

This is targeted therapyPatient with late-stage or unresectable melanomaGenetic testing of tumor DNA – targeted test for acquired BRAF V600E missense mutation in tumor cellsPatient is a candidate for vemurafenib therapy ONLY if BRAF V600E is present. (Drug is not effective against normal BRAF protein.)

Question 27

What is the basis of a liquid biopsy?

Answer 27

In a tumor patient, there is cell free DNA from the tumor in the blood. You can take blood sample and look for mutations, sequence, etc. to identify the cancer