random path stuff to know

Question 1

esophageal squamous cell carcinoma mutations

Answer 1

amplification of SOX2 (cancer stem cell renewal)
over expression of cyclin D1 (cell cycle regulator)
loss of function in TP53, e-cadherin, and NOTCH1 (tumor suppressors)

Question 2

esophageal adenocarcinoma mutations

Answer 2

early: TP53 mutation, down regulation of CDKN2A (p16/INK4a)
later: amplification of EGFR, ERBB2, MET, cyclin D1, and cyclin E genes

Question 3

intestinal type gastric adenocarcinoma

Answer 3

Increased signaling in the Wnt pathway:
loss of function in APC (tumor suppressor)
gain of function in beta-catenin

TGFbRII loss of function (TGF-beta regulator)
BAX loss of function (apoptosis)
CDKN2A loss of function (cell cycle control)

Question 4

familial adenomatosis polyposis (FAP)

Answer 4

germline APC mutation

Question 5

diffuse type gastric adenocarcinoma

Answer 5

loss of function of CDH1 (encodes E-cadherin)
BRCA2 mutations
TP53 mutation

Question 6

hereditary pancreatitis

Answer 6

CTFR loss of function (inspissation of secreted fluids leading to duct obstruction)
PRSS1 gain of function (trypsin mutations)
SPINK1 loss of function (inhibitor of trypsin)

Question 7

progression to invasive pancreatic carcinoma

Answer 7

early: activating KRAS (most common oncogene in pancreatic cancer) and telomere shortening
intermediate: inactivation of CDKN2A (cell cycle regulator p16; most common tumor suppressor inactivated in pancreatic cancer)
high grade: TP53, SMAD4, and BRCA2

Question 8

Peutz-Jegher’s syndrome mutation

Answer 8

STK11

Question 9

Familial atypical multiple-mole melanoma syndrome mutation

Answer 9

CDKN2A

Question 10

mutation in majority of both intestinal and diffuse gastric cancer

Answer 10

TP53

Question 11

APC pathway to colon cancer

Answer 11

APC/beta-catenin mutations –> KRAS –> TP53

Question 12

MSI pathway to colon cancer

Answer 12

mutations in micro satellite repeat regions+defects in DNA repair –> TGF-beta receptor, BAX (apoptosis gene), and BRAF

Question 13

hepatocellular carcinoma marker

Answer 13

alpha fetoprotein

Question 14

HNF1-alpha inactivated subtype of hepatocellular adenoma

Answer 14

lack of LFABP expression

Question 15

beta-catenin activated subtype of hepatocellular adenomas

Answer 15

nuclear translations of beta-catenin , indicative of the active state

Question 16

inflammatory subtype of hepatocellular adenomas

Answer 16

activating mutations in gp130, a co-receptor for IL-6 that leads to constitutive JAK-STAT signaling and over expression of acute phase reactants

Question 17

cholangiocarcinoma

Answer 17

intrahepatic: KRAS mutation in 50%
extrahepatic: KRAS in 15%
p53 mutation in 33%

Question 18

hepatocellular carcinoma mutations

Answer 18

inactivation of p53 in 60%
activation of beta-catenin in 40%
signaling through the IL-6/JAK-STAT pathway

Question 19

NASH

Answer 19

hedgehog signaling

Question 20

Gastric neuroendocrine tumor

Answer 20

Synaptophysin and chromogranin positive

Question 21

hemochromotosis

Answer 21

C282Y mutation in HFE gene

Question 22

Wilson’s disease

Answer 22

autosomal recessive deficiency of ATPase, preventing the conversion of copper to ceruloplasmin

Question 23

glycogen storage disease type 1 (von gierke)

Answer 23

deficiency of glucose-6-phosphatase

Question 24

tyrosinemia type 1

Answer 24

fumaryl-aceto-acetase defeiciecy

Question 25

Gaucher’s disease

Answer 25

deficiency of beta-glucocerebrosidase

Question 26

acute intermittent porphyria

Answer 26

autosomal dominant deficiency of porphobilinogen-deaminase

Question 27

primary biliary cirrhosis

Answer 27

anti-mitochondrial antibodies

Question 28

pancreatic serous cystic neoplasm

Answer 28

VHL mutation

Question 29

pancreatic mutinous cystic neoplasm

Answer 29

KRAS and TP53 most commonly mutated

Question 30

GI stromal tumor

Answer 30

early: KIT activation (CD117+)
Late: loss oc CDKN2A (p16)

Question 31

GI lymphoma translocations

Answer 31

11;18 - API2-MLT
1;14 - increases MALT1 expression
14;18 - increases BCL-10 expression
all three lead to constitutive activation of NFkB promoting B cell growth and survival

Question 32

GI lymphoma transformation to diffuse large B cell lymphoma

Answer 32

TP53

Question 33

cause of post-transplant proliferative disorder

Answer 33

immunosuppression allows EBV to proliferate

Question 34

crohn’s disease mutation

Answer 34

NOD2 - activates NFkB signaling

ATG16L1 and IRGM: autophagy pathway

Question 35

celiac disease susceptibility

Answer 35

HLA-DQ2/8

Question 36

ulcerative colitis

Answer 36

ECM1 polymorphisms (responsible for MMP9 regulation/inhibition)
HNFA polymorphisms