Hereditary cancer and faulty DND repair syndromes

Question 1

what types of neoplasms are associated with lynch syndrrome?

Answer 1

colorectal cancer
endometrial cancer
ovarian cancer

lynch syndome = hereditary non-polyposis colorectal cancer

Question 2

what genes are associated with lynch syndrome?

Answer 2

MSH2
MLH1
MSH6
PMS2

Question 3

what is the mechanism for lynch syndrome?

Answer 3

autosomal domonant INACTIVATING mutation of a tumor suppressor genes (RESPONSIBLE FOR MISMATCH REPAIR) — leads to microsatellite insitibility of DNA

deletion of the remaining normal allele (second hit) leads to loss of heterozygosity and malignant transformation

Question 4

what neoplasms are associated with familial adenomatous polyposis?

Answer 4

colorectal cancer
desmoids and osteomas
brain tumors

Question 5

what gene is associated with familial adenomatous polyposis?

Answer 5

APC

Question 6

what is the mechanims for familial adenomatous polyposis?

Answer 6

inactivating mutation of tumor supressor gene along with second hit loss of heterozygosity and malignant transformation

Question 7

what types of neoplasms are associated with von-hippel lindau syndrome?

Answer 7

hemangioblastomas
clear cell renal cell carcinoma
pheochromocytoma

Question 8

what causes von hippel lindau ?

Answer 8

mutation of VHL gene , loss of tumor supressor + deletion of remaining allele and loss of heterozygosity leads to malignant transformation

Question 9

what neoplasms are associated with li-fraumeni syndome?

Answer 9

sarcomas
breast cancer
brain tumors
adrenocortical carcinoma
leukemia

Question 10

what gene is fucked up in le-fraumeni sysndome?

Answer 10

TP53 – inactivating mutation of a tumor supressor gene ==> second hit causes malignant trandformation due to loss of remainng normal allele

Question 11

what gene is fucked up in multiple endocine neoplasea 1? WHat is the mechanism for development of parathyroid adenomas, pituitary adenomas, and pancreatic adenomas?

Answer 11

MEN1
inactivating mutation of a tumor supressor gene ==> second hit causes malignant trandformation due to loss of remainng normal allele

Question 12

what is fucked up in multiple endocrine neoplasea 2?

what is the mechanism?

Answer 12

RET - activating (gain of function) mutation in proto-oncogene leading to continuous stimulation of cell devisions

leads to medulary thryroid cancer (solitary thryoid nodule) hyperparathyroidism and pheochromacytoma

Question 13

what gene?
hemangioblastomas
clear cell renal cell carcinoma
pheochromocytoma

Answer 13

VHL

von-hippel lindau

Question 14

what gene? What syndrome? 
sarcomas
breast cancer
brain tumors
adrenocortical carcinoma
leukemia

Answer 14

TP53

li-fraumeni

Question 15

what gene? what syndrome?

colorectal cancer
desmoids and osteomas
brain tumors

Answer 15

APC

familial adenomatous polyposis

Question 16

what gene? what syndrome?
colorectal cancer at an early age that most commonly affects the proximal bowel
endometrial cancer
ovarian cancer

Answer 16

MSH2
MLH1
MSH6
PMS2

lynch syndrome

Question 17

what does elevated CA-125 indicate?

Answer 17

ovarian cancer

Question 18

what is fucked up in ataxia-telangiectasia?

Answer 18

ATM gene mutationn leads to inactivation of tumor supressor p53, reuslting is disruption of the non-homologous end joining repair mechanism

this mechanism is particularly important in repairing damage due to ionizing radiation

Question 19

what is most likely associated neoplasm for ataxia-telangiectasia?

Answer 19

primary CNS lymphoma and leukemia

Question 20

what disorder is characterized by failure to repair cyclobutane pyrimidine dimers?

Answer 20

xeroderma pigmentosum

defective nucleotide excision repair mechanisms

autosomal recessive

Question 21

what are the clinical symptoms of xeroderma pigmentosum?

Answer 21

photosensitivity, increased pigmentation, xerosis (abnormal skin dryness).

Question 22

what are pts with xeroderma pigmentosum at increased risk for?

Answer 22

Corneal ulcers and cutaneous malignancies:

squamous cell carcinoma
basal cell carcinoma
melanoma

treatment is with complete avoidance of sunlight

Question 23

pt presents with 
    short stature
    rash from sun exposure
    predisposed to lymphoproliferative and gastrointestinal malignancies 
what do they have?

Answer 23

Bloom syndrome

may also have café-au-lait spot or tangelectasias

Question 24

what’s the cause of bloom syndome?

Answer 24

lack of BLM helicase enzyme due to defective RecQL3 gene - impaired homologous recombination

BLM helicase is normally involved in repairing double-strand breaks

requires a sister chromatid to use as a template

therefore must occur after S phase of cell cycle

Question 25

what type of repair mechanism is used to fix when the bond between the sugar backbone and the nucleotide (glycosidic bond) has been severed?

Answer 25

base excision repair (BER) The BER pathway starts off with a DNA glycosylase recognizing and removing the damaged base. An apurinic/apyrimidinic endonuclease cleaves the backbone, removing the remaining sugar fragment. The gap is then filled by the cell's DNA replication machinery - DNA polymerase and ligase.

Question 26

what type of repair mechanism corrects damage done from UV-B light?

Answer 26

Nucleotide Excision Repair - removes thymidine dimers

Question 27

what gene mutation occurs in hereditary retinoblastoma?

Answer 27

Rb defect - loss of inhibition of E2F permits S phase gene transcription and malignant transformation N-myc may also be involved