Cancer Genetics Flashcards
Exam 2
Gene mutation is inherited in family; significantly increased cancer risk
Hereditary
Multiple genes & environmental factors may be involved; some increase in cancer risk
familial
cancer occurs by chance or related to environmental factors; general population cancer risk
sporadic
loss of normal growth control
cancer
cancer is caused by a
cascade of genetic alterations
two acquired mutations
sporadic cancer
one inherited, one acquired mutation
hereditary cancer
if first hit is a germline mutation, second somatic mutation more likely to enable
Cancer
promote cell growth
oncogenes
inhibit cell cycle and promote apoptosis
suppressor genes
correct replication errors
mismatch repair genes
tumor suppressor genes
restrain cell growth
mismatch repair genes
maintain correct DNA sequences
Mismatch repair genes (3)
(1) MLH1 (2) MSH2 (3) MSH6
Tumor suppressor genes (4)
(1) Rb (2) NF1 (3) p53 (4) APC
loss of both copies needed to cause cancer
loss of function
a single somatic gene mutation can cause cancer
gain of function
oncogenes is a
gain of function
Oncogenes (3)
(1) RET (2) BCR-ABL (3) HRAS
RET
lung, multiple endocrine neoplasia
BCR-ABL
leukemia
HRAS
costello
Higher cancer risk is inherited as an
Autosomal Dominant trait
Hareditary cancer associated with (2)
(1) incomplete penetrance (2) variable expressivity
hereditary cancer red flags
combinations of certain cancer
multiple genes can increase the risk of a
single cancer
can be associated with a single genes
multiple cancers
General Population: Breast
12%
General Population: ovarian
1-2%
General Population: male breast
.10%
General Population: prostate in erupean vs african American
European- 15% African American- 18%
General Population: pancreatic
.50%
BRCA1/BRCA2: Breast
50-80%/ 40-70%
BRCA1/BRCA2: ovarian
24-40%/ 11-18%
BRCA1/BRCA2: male breast
1-2%/ 5-10%
BRCA1/BRCA2: prostate
30%/ 39%
BRCA1/BRCA2: pancreatic
1-3%/ 2-7%
all three receptors: BRCA, progesterone, estrogene are not working
triple negative breast cancer
more children increased risk for
BRCA1
colorectal cancer: normal epi.—-> adenoma
APC
colorectal cancer: adenoma—> late adenoma
K-ras
colorectal cancer: late adenoma ——> early cancer
p53
colorectal cancer: optimum phase for early detection
late adenoma—>early cancer 2-5 years
associated in size and dysplasia
K-ras
lynch syndrome
colorectal cancer
limitations of unknown significance
-variants of unknown significance - negative test result mutation increases cancer -suspetibility
who is the most informative person to test?
Person B
2.What is our patient’s risk for having inherited the same BRCA2 variant?
25%
3.Would you test our patient for the TP53 variant?
No
4.For the paternal side of the family: Which of the following is not considered a red flag for a hereditary cancer syndrome?
A.Colon cancer diagnosed at 48y
B.Ovarian cancer diagnosed at 79y
C.Ashkenazi Jewish ancestry
D.Combination of cancers
E.None of the above
E.None of the above
