Chapter 7 - Neoplasia

Question 1

ERBB1 gene

Answer 1

Oncogene - Encodes epidermal growth factor receptor (EGFR)

Question 2

ERBB2 gene

Answer 2

Oncogene - Encodes HER2

Question 3

EML4-ALK fusion gene

Answer 3

Oncogene - Deletion on chromosome 5 fuses part of the ALK gene with the EML4 gene. Subset of lung adenocarcinomas

Question 4

The 3 human RAS genes

Answer 4

HRAS, KRAS, and NRAS

Question 5

Neurofibromin 1

Answer 5

GTPase-activating protein encoded by tumour suppressor gene NF1. Disabling mutations -> familial neurofibromatosis type 1

Question 6

BRAF

Answer 6

Member of RAF family of serine/threonine protein kinaese. MAPK signalling cascade

Question 7

PTEN

Answer 7

Tumor suppressor - negativity regulates PI3K signaling cascade

Question 8

Oncogene addiction

Answer 8

Tumor cell dependence on the activity of one oncoprotein

Question 9

BCR-ABL protein

Answer 9

Chimeric protein formed by ABL gene translocation from chromosome 9 to chromosome 22, fusing with the BCR gene - constitutively active tyrosine kinase. Seen in CML

Question 10

JAK2

Answer 10

Nonreceptor tyrosine kinase. Participates in JAK2/STAT signaling pathway.

Question 11

MYC gene

Answer 11

Proto-oncogene - Encodes pro cell growth transcription factor. Rapidly and transiently induced by RAS/MAPK pathway.

Question 12

Li-Fraumeni syndrome

Answer 12

Inheritance of one mutated copy of TP53 gene. 25x greater chance of developing a malignant tumor by age 50

Question 13

E6 protein

Answer 13

Viral oncoprotein that bind p53 (protein encoded by TP53 gene) and promote its degradation. Found in high-risk HPVs (such as HPV16)

Question 14

ATM and ATR proteins

Answer 14

Ataxia-telangiectasia mutated, and ataxia-telangiectasia and Rad3 related. Disrupt MDM2 inhibition of p53 during hypoxia and DNA damage.

Question 15

p14/ARF protein

Answer 15

Encoded by CDKN2A tumor suppressor gene. Bind MDM2 and displaces p53, allowing p53 levels to rise. Seen during oncogenic stress.

Question 16

p53

Answer 16

Encoded by TP53 tumor suppressor gene. Transcription factor of target genes that cause:
1) Cell cycle arrest
2) Apoptosis
3) enhance catabolic metabolism and inhibit anabolic metabolism

Question 17

CDKN1A gene

Answer 17

Encodes p21 by p53-dependent transcription. CDK4/cyclin D inhibitor -> RB remains active

Question 18

APC protein

Answer 18

Adenomatous polyposis coli. Component of WNT signaling pathway. Down regulate growth promoting signals. Germline loss-of-function mutation -> Familial adenomatous polyposis

Question 19

CDKN2A gene

Answer 19

Encodes both p16/INK4a and p14/ARF

Question 20

Cowden syndrome

Answer 20

Mutated Phosphatase and tensin homologue (PTEN). Membrane-associated phosphatase. Autosomal dominant leading to frequent benign skin appendage growth and epithelial cancers.

Question 21

How does hypoxia effect HIF1a?

Answer 21

Hydroxylation that binds HIF1a to VHL does not occur. HIF1a accumulates and turns on target genes like VEGF (vascular endothelial growth factor), PDGF (mitogen), GLUT1 and factors contributing to Warburg metabolism.

Question 22

Peutz-Jeghers syndrome

Answer 22

Loss of function mutation to STK11 gene. Autosomal dominant disorder with benign polyps of GI tract and increased risk of epithelial cancers.