Neoplasms/ Cancer disorders

Question 1

Change in bowel habits, constipation, decreased stool caliber, difficulty passing stools, blood in stool, gross occult blood in stool, and iron deficiency anemia are signs and symptoms of what?

Answer 1

colorectal cancer

Question 2

Colon cancer is the third most common cancer in males and females. True or false?

Answer 2

True

Question 3

Hispanics have the highest incidence of colorectal cancer compared to Blacks and Caucasians. True or false?

Answer 3

FALLSSEE!

They have the lowest incidence of colorectal cancer compared to Blacks and Caucasians.

Blacks have the HIGHEST incidence rate of colorectal cancer.

Question 4

What is the second leading cause of cancer death in US?

Answer 4

colorectal cancer

Question 5

Colon cancer based on localized, regional, and distant stage. What does distant stage refer to?

Answer 5

metastasis

You would optimally want to detect the cancer while its still in the localized stage.

Question 6

The risks of having colorectal cancer begins at the age of 50 for the general population. What about for African Americans?

Answer 6

45 years of age

Question 7

The prevalence of colorectal cancer is decreasing or increasing in African American young adults? What are some factors that contribute to this finding?

Answer 7

increasing

• environment
• behavior
• genetics

Question 8

Hereditary nonpolyposis colorectal cancer is also known as?

Answer 8

Lynch syndrome

Question 9

The majority of colorectal cancers are of what type?

Answer 9

sporadic

follows by familial, then Lynch syndrome, then familial adenomatous polyposis

Question 10

What does FAP stand for?

Answer 10

familial adenomatous polyposis

Question 11

FAP is only APC. What does this mean?

Answer 11

FAP is monogenic.

APC= Adenomatous polyposis coli

Question 12

Ras, PI3K, STAT, MAPK, and TGF-beta are all examples of what that regulate cell survival? NOTCH, HH, and APC are all examples of what that regulate cell fate?

Answer 12

Ras, PI3K, STAT, MAPK, and TGF-beta are oncogenes.

NOTCH, HH, and APC are tumor suppressors.

Question 13

What are MSI and MSS?

MSI= microsatelite instability 
MSS= microsatelite stability

Answer 13

They are two different types of colorectal cancer. They both require DIFFERENT treatments which brings up the importance to subtype colorectal cancers.

Hypermutability of cancer in MSI is important for treatment, management, and intervention of the disease. This is why sequencing very important.

Question 14

Amino acids changes primarily occur in what region of the gene for colon cancer?

Answer 14

coding regions

Colorectal cancer is the # 1 cancer you can detect 100% meaning you can prevent 100% by SCREENING.

Question 15

What are the 3 methods of gene silencing in normal cells and what phenomenon to they represent?

Answer 15

DNA methylation
Histone modifications
Nucleosome remodeling

They all represent epigenetics where there is no change in the DNA strand.

Question 16

In colon cancer, genes such as mixmatch repair genes become methylated and silenced. What is the result of this?

Answer 16

The mutated genes in colon cancer cannot be repaired thus advancing the cancer.

Question 17

For the detection of DNA methylation in colon adenoma and colon carcinoma, what are the biomarkers used respectively?

Answer 17

Vimentin for colon adenoma
Sept9 for colon carcinoma

This is a NON-INVASIVE detection of colon cancer.

Question 18

What is the most commonly used fecal occult blood test?

Answer 18

fecal immunochemical test (FIT)

Question 19

What oncogene is tested for in the lab for the progression of colon cancer and why?

Answer 19

KRAS because it has actionable and draggable values. They know that if it is mutated, they cannot use cetuximab (anti-EGFR).

Question 20

In the lab in the past, scientists would observe the pathology of cancer under a microscope but now this is heavily used for precision medicine.

Answer 20

biomarkers

Question 21

What is the difference in therapeutic targets between chromosomal instability (CIN) and microsatelite instability (MIN)?

Answer 21

MLH1 (mixmatch repair gene) hypermethylation and BRAF (an oncogene) activation in MIN

Loss of APC and KRAS activation in CIN

Both epigenetic and genetic plays a role in the progression of colorectal cancer.

Question 22

In lynch syndrome AKA HNPCC, what are the two highest mutated genes?

Answer 22

MLH1 30%
MSH2 30%

30% of the pie chart for Lynch syndrome is still unknown that is why it is important to continue doing research for these unknowns.

Question 23

Sessile Serrated Polyp/Adenoma illustrates an example as to why these are being used for detection of colon cancer.

Answer 23

biomarkers: in this case CIMP= CpG island methylator phenotype

In the past, pathologist would disregard flat polyps in colon biopsy. However, these flat polyps are a part of sessile serrated adenomas (one type of colon adenoma) which are much more aggressive and become cancer.

Question 24

Adenomas are precursors for cancer. So you need to understand that there are subtypes.

Answer 24

You can catch them with the markers and have the right intervention for them.

Question 25

Picture can differentiate between sessile serrated adenomas and traditional serrated adenomas. True or false?

Answer 25

FAALLLSEEE!!!

You cannot tell the difference between their images. However you can detect difference in their biomarkers during detection.

Question 26

What’s the percentage of colorectal cancers that are hereditary, familial, and sporadic respectively?

Answer 26

5-8% of all cases of CRC are hereditary

15-20% are “familial” / multifactorial

75% of cases are sporadic

Question 27

A rare germline mutation in this gene will primarily cause familial adenomatous polyposis (FAP) adenomas as the estimated penetrance is 90%.

Remember FAP is autosomal dominant.

Answer 27

APC gene

APC= adenomatous polyposis coli

Question 28

The majority of mutations in the APC gene in this exon cause full blown FAP.

Answer 28

exon 15

Question 29

What signaling pathway triggers colon cancer?

Answer 29

Activated Wg/Wnt signaling

Beta-catenin does not degrade in the Wg/Wnt signaling and goes to the nucleus and starts activating proliferative gene.

Question 30

What is the difference between full FAP and attenuated FAP?

Answer 30

Full FAP
Estimated penetrance for adenomas >90%
Risk of extracolonic tumors (upper GI, desmoid, osteoma, thyroid, brain, other)
CHRPE may be present
Untreated polyposis leads to 100% risk of cancer

Attenuated FAP (seen in Ashkenazi Jews)
Later onset (CRC ~age 50)
Few colonic adenomas
Not associated with CHRPE
UGI=Upper GI lesions 
Associated with mutations at 5' and 3' ends of APC gene

Question 31

For HNPCC you don’t see polyps early on so it has a late detection rate. Which gene is mutated in HNPCC?

Answer 31

Mutation in one of several DNA mismatch repair genes
and 90% of the time due to replication error thus microsatelite instability

MLH1 mixmatch repair gene is the most mutated mixmatch repair gene

Question 32

Screening for HCPCC is important because increase in the number of affected relative increases your risk of having HCPCC. True or false?

Answer 32

True!!!

General Population 6%
One 1st degree relative 2-3 fold increase
Two 1st degree relatives 3-4 fold increase
One 1st degree relative (>50 y/o) 3-4 fold increase
One 2nd or one 3rd degree relative approx 1.5 fold
increase
Two 2nd degree relatives 2-3 fold increase

Question 33

What is the difference between selective and universal screening for Lynch syndrome?

Answer 33

Selective: test <50 years of age

Universal: test regardless of age (this is a better method AKA he said “good centers” do these)