10.2 Cancer Highlights

Question 1

What are 2 origins of cancer?

Answer 1

1) Sporadic: genetic mutation of single somatic cell
2) Inherited (familial)

Question 2

When cancer occurs as part of a ______________ cancer syndrome, the __________ cancer-causing mutation is inherited through the germline

Answer 2

hereditary; initial

Question 3

1) The development of cancer is called what?
2) Are most cancers inherited or sporadic?

Answer 3

1) Oncogenesis
2) Sporadic

Question 4

1) Cancer cells are clonal descendants from how many mutant cells?
2) The cell accumulates many specific mutations over a long period of time; hence, _______ as the primary risk factor for cancer
3) Cancer cells escape control of the cell cycle and begin uncontrolled division and ___________ continue to accumulate

Answer 4

1) one mutant cell
2) age
3) mutations

Question 5

____________ is a disease process characterized by uncontrolled cellular proliferation leading to the growth of a tumor (neoplasm)

Answer 5

Neoplasia

Question 6

For a tumor to be cancer, it must also be ______________, which means it is capable of spreading or metastasizing to other locations

Answer 6

malignant

Question 7

What are 2 primary characteristics of cancer?

Answer 7

invasive and malignant

Question 8

A process by which cells detach from the primary tumor and move to other sites in the body is called what?

Answer 8

Metastasis

Question 9

Benign tumors are usually designated by adding what to cell type of origin?

Answer 9

“-oma”

Question 10

1) What are carcinomas?
2) What is adenocarcinoma?
3) What is SCC?

Answer 10

1) Arise in epithelial tissue*
2) Malignant tumor of glandular cells
3) Malignant tumor of squamous cells

Question 11

List where each arises:
1) Sarcomas
2) Leukemias
3) Lymphomas

Answer 11

1) Mesenchymal tissue
2) Hematopoietic cells
3) Lymphoid tissue

Question 12

For benign tumors, describe their:
1) Growth
2) Metastasis
3) External surface
4) Capsule
5) Necrosis
6) Hemorrhage

Answer 12

1) Slow, expansive
2) No
3) Smooth
4) Yes
5) No
6) No

Question 13

Why does a cancerous mass bleed so much?

Answer 13

Because it can’t create enough blood supply to supply the cells in the middle of the mass, so they die

Question 14

For malignant tumors, describe their:
1) Growth
2) Metastasis
3) External surface
4) Capsule
5) Necrosis
6) Hemorrhage

Answer 14

1) Fast, invasive
2) Yes
3) Irregular
4) No
5) Yes
6) Yes

Question 15

For benign tumors, describe their:
1) Architecture
2) Cells
3) Nuclei
4) Mitoses
5) Chromosomes

Answer 15

1) Resembles original tissue
2) Well differentiated
3) Normal size + shape
4) Few
5) Normal

Question 16

For malignant tumors, describe their:
1) Architecture
2) Cells
3) Nuclei
4) Mitoses
5) Chromosomes

Answer 16

1) Doesn’t resemble tissue of origin
2) Poorly differentiated
3) Pleomorphic
4) Many irregular
5) Aneuploid

Question 17

List 4 malignant tumors that sound benign

Answer 17

1) Lymphoma
2) Mesothelioma
3) Melanoma
4) Seminoma

Question 18

List + define 2 non-tumors that sound like tumors

Answer 18

1) Hamartoma: mass of disorganized indigenous tissue
2) Choristoma: heterotopic mass of cells

Question 19

1) Genes that initiate or maintain cell division are called what?
2) Mutant genes that induce or continue uncontrolled cell proliferation are called what?

Answer 19

1) Proto-oncogenes
2) Oncogenes

Question 20

ras Proto-Oncogene
1) What does it do when active?
2) What does it do when inactive?

Answer 20

1) Transfers molecular signals from the plasma membrane to the cell nucleus and initiates cell division
2) Cell division is inhibited

Question 21

1) Genes that mediate programmed cell death are called what?
2) Genes that help maintain the integrity of the genome are called what? Give an example

Answer 21

1) Gatekeeper TSGs
2) Caretaker genes; DNA repair genes

Question 22

*Tumor suppressor genes:
1) What proteins do these encode?
2) Deletion or inactivation of these products cause cells to do what?
3) _____________ mutations in tumor suppressor genes cause cancer (Two-hit hypothesis)

Answer 22

1) Those
2) Divide continuously
3) Recessive

Question 23

Cyclin Dependent Kinases AND Cyclin Dependent Kinase Inhibitors (CDKIs)

Answer 23

1) Cyclin Dependent Kinases drive the cell cycle by combining with cyclins to move from one phase to the next
2) CDKIs are inactivated in many cancers (TSGs)

Question 24

1) Cyclin Dependent Kinases drive the cell cycle by doing what?
2) Cyclins are _____________ in many cancers(oncogenes)
3) While CDKIs are _____________ in many cancers(TSGs)

Answer 24

1) combining with cyclins to move from one phase to the next
2) overexpressed
3) inactivated

Question 25

*1) ___________ is a tumor suppressor gene that monitors cellular stress (usually referred to as just ______) 2) What is activated by anoxia, inappropriate oncogene signaling, or DNA damage? * = also MJ slide

Answer 25

1) TP53; p53 2) P53

Question 26

1) *P53 _____________ neoplastic transformation by several mechanisms 2) List these 3 mechanisms

Answer 26

1) prevents 2) repair, arrest, death

Question 27

*TSG Mutations Occur in both ___________ and ___________Forms

Answer 27

Hereditary and Sporadic

Question 28

1) Cancer is initiated when a second inactivating mutation occurs in the __________ TSG allele in one cell of the body. 2) Cancer is initiated when both normal alleles are inactivated by ______ somatic events in the same cell.

Answer 28

1) normal 2) two

Question 29

Retinoblastoma is a _______________ tumor of the eye arising in retinoblasts (embryonic retinal cells that disappear at about 2 years of age)

Answer 29

malignant

Question 30

Because mature retinal cells do not transform into tumors, this tumor usually occurs only in _____________ and is caused by mutations in the _______ gene on chromosome ________--.

Answer 30

children; RB1; 13

Question 31

*What are 2 kinds of retinoblastoma? Differentiate between their genetics

Answer 31

1) Familial (hereditary) -one mutant copy of RB1 gene and one normal copy of the RB1 gene -normal copy of RB1 gene acquires a spontaneous mutation 2) Sporadic -mutations of both copies of RB1 gene occur in a single cell

Question 32

*Hereditary retinblastoma 1) With hereditary retinoblastoma, there's a _________ to _________% chance of developing the disease 2) Where/ when does it usually occur? Why?

Answer 32

1) 85-95% 2) Usually both eyes; because both eyes have already had one mutation, so each just needs one more mistake for disease to occur

Question 33

*Sporadic retinoblastoma: When does it usually occur and why?

Answer 33

Usually involves one eye and has a later onset

Question 34

*True or false: All patients with bilateral disease have germline RB1 mutations, but not all patients with germline mutations develop bilateral disease.

Answer 34

True

Question 35

*Retinoblastoma is uniformly __________ if untreated, so CHECK THE ______ REFLEX!!!

Answer 35

fatal; RED

Question 36

*Retinoblastoma: 1) Given appropriate therapy, more than ____ to ____% of patients are free of disease 5 years after diagnosis. 2) Patients with _______________ mutations have a markedly increased risk of secondary neoplasms.

Answer 36

1) 80% to 90% 2) germline RB1

Question 37

If the disease is unilateral at the time of the patient's presentation, the patient still needs frequent examinations to detect any new retinoblastomas in the unaffected eye because ____% of apparently sporadic cases are caused by the inheritance of a new germline mutation

Answer 37

30%

Question 38

*Lynch syndrome: 1) A form of colon cancer that develops with very few ________, but each with a high probability of becoming _________. 2) An autosomal caretaker mutation caused by mutations in one of four DNA __________ repair genes

Answer 38

1) polyps; cancerous 2) mismatch

Question 39

Patients with Lynch syndrome are also at increased risk for cancers of what origin(s)?

Answer 39

Ovary, stomach, small intestine, pancreas, upper urinary tract, hepatobiliary tract, brain, skin, and prostate

Question 40

Lynch syndrome: 1) Mutations in MMR genes generate a cascade of mutations in DNA microsatellites, which does what? 2) Mutations in microsatellites that are in or near other genes disrupt what?

Answer 40

1) destabilizes the genome 2) the functions of those genes

Question 41

**Lynch syndrome:** Current guidelines recommend that all patients with __________ have their tumors screened for LS, and patients with positive tumors should be offered genetic counseling and genetic testing for LS

Answer 41

CRC

Question 42

Lynch Syndrome: 1) When should you start surveillance colonoscopy? 2) What abt transvaginal ultrasound?

Answer 42

1) 20-25 2) 30-35

Question 43

In oncogenesis, a single cell acquires ___________ mutations and failure of regulation to become a cancer

Answer 43

several

Question 44

Give the short version of step 1 of tumorigenesis

Answer 44

[mutations in] activated oncogenesis + tumor-suppressor genes = no growth factor needed, escaped cell cycle

Question 45

Step 2 of tumorigenesis (short version)

Answer 45

Failure to stop either of the two mutations

Question 46

Step 3 of tumorigenesis (short version)

Answer 46

Express MHC I proteins to decrease immune response Evade CD4 T cells and NK cells

Question 47

Step 4 of tumorigenesis (short version)

Answer 47

Antiapoptic genes don't work,

Question 48

Step 5 of tumorigenesis (short version)

Answer 48

Immortality is created due to antiapoptic genes not working, telomerase

Question 49

Step 6 of tumorigenesis (short version)

Answer 49

VEGF (Vascular endothelial growth factor) leads to "All you can eat” blood supply

Question 50

What is step 7 of tumorigenesis? (short version)

Answer 50

Metastasis

Question 51

Tumorigenesis: Step 2 (Fail to regulate mutation)

Answer 51

a) Loss of miRNAs that fail to downregulate oncogenes leads to overexpression of the oncogene b) Activation of miRNAs that downregulate TSGs leads to loss of TSG expression

Question 52

Tumorigenesis: Step 3

Answer 52

MHC I presents “self antigen” to T cells + also inhibits the cytotoxic effects of Natural Killer Cells

Question 53

Tumorigenesis: Step 4

Answer 53

Escape Apoptosis: BCL2 normally keeps cytochrome C within the mitochondria; IAP/ “Inhibitor of Apoptosis Protein” blocks the intrinsic apoptosis cascade (Remember, this is the means through which damaged DNA is regulated)

Question 54

Tumorigenesis: Step 5

Answer 54

Become Immortal: The CA cells produce telomerase to extend the life of the cell, so that **senescence never occurs**

Question 55

Tumorigenesis: Step 6

Answer 55

Create Blood Supply: 1) Tumor makes VEGF 2) Tumor needs more blood; it can achieve this increased supply by getting more vessels to its site

Question 56

Tumorigenesis: Step 7 (Metastasize) 1) A further consequence of VEGF expression is that _____________________ aids the spread of the tumor through local invasion and distant metastasis. 2) This happens because the cells lack polarity and are rapidly _________________ 3) They are friable, therefore, and able to move to distant sites through the available blood supply, especially after passing through the local __________________________. 4) Often, the cancer cells are taken up by the _______________ system

Answer 56

1) neo-vascularization 2) proliferating 3) basement membrane 4) lymphatic

Question 57

1) Deletion or duplication of entire chromosomes, or chromosome segments, respectively are called what? 2) Define Gene Amplification 3) The exchange of segments between chromosomes are what?

Answer 57

1) Aneuploidy and Aneusomy 2) Segments of chromosomes are replicated multiple times 3) Chromosomal translocations

Question 58

*What are the 7 things that make cancer cells different from other cells?

Answer 58

They: 1) Grow and proliferate without regulation by escaping the cell cycle 2) Fail to regulate initial mutation 3) Escape our own immune System 4) Escape the Apoptosis pathway 5) Become immortal after making telomerase 6) Create their own blood supply 7) Then invade other tissues

Question 59

True or false: environment can affect carcinogenesis

Answer 59

True

Question 60

Human Papillomaviruses cause _________ cancer

Answer 60

cervical

Question 61

Grading and staging: differentiate between them

Answer 61

1) Grading: Cytological evaluation of tumor 2) Staging: Size of primary lesion and extent of metastases

Question 62

Tumor staging incorporates what 3 things?

Answer 62

1) Size of the primary tumor 2) The presence of lymph node spread 3) Distant metastases

Question 63

What is TNM?

Answer 63

TNM T (primary tumor): TX, T0, T1, T2, T3, T4 N (regional lymph nodes): NX, N0, N1, N2, N3 M (metastasis): Mx, M0, M1

Question 64

True or false: Some cancers are grouped into five stages (0-IV)

Answer 64

True (0 = abnormal, 4 = metastasis)

Question 65

Name a morphologic method for diagnosing cancer

Answer 65

Biopsy

Question 66

The hallmark of a cancerous growth is what?

Answer 66

metastasis