Cancer + cancer conditions Flashcards
(102 cards)
1
Q
What types of cells are affected by carcinomas?
A
epithelial cells
2
Q
What type of cells are affected by adenocarcinomas?
A
gland epithelial cells
3
Q
What types of tissues are affected by sarcomas?
A
blood, muscle, bone (mesoderm origin)
4
Q
What are the stages of the cell cycle?
A
G1- growth, no DNA synthesis
G0- cell division arrested (blood cells, neurons)
S- DNA replication
G2- cell growth
M- mitosis
5
Q
Are mutations in oncogenes and tumor suppressor genes GOF or LOF?
A
oncogenes: GOF
TS: LOF
6
Q
What are the AJ BRCA founder mutations?
A
BRCA1 187delAG
BRCA1 5385insC
BRCA2 6174delT
7
Q
What moderate risk hereditary breast cancer gene also includes an increased risk for male breast cancer?
A
PALB2
8
Q
What is the general population risk for CRC by age 80?
A
4%
FDR- 9%
>1 FDR- 16%
9
Q
What are the polyp type criteria for NCCN?
A
> = 10 adenomatous
= 2 hamartomatous
= 5 serrated proximal to rectum
10
Q
What section of the colon is more likely to be affected by Lynch syndrome related CRC?
A
transverse and ascending
11
Q
What other gene does MLH1 form a complex with?
A
PMS2
12
Q
What other gene does PMS2 form a complex with?
A
MLH1
13
Q
What other gene does MSH6 form a complex with?
A
MSH2
14
Q
What other gene does MSH2 form a complex with?
A
MSH6
15
Q
What gene in the MMR pathway has the lowest cancer risks?
A
PMS2
16
Q
How does EPCAM lead to increased cancer risk?
A
deletion in 3’ area –> hypermethylation and silencing of MSH2
17
Q
What are symptoms of hemangioblastomas in VHL?
A
causes pressure–> headaches, visual changes, pain, vomiting
80% brain 20% spinal cord
18
Q
What is the classic triad associated with MEN1 cancer syndrome?
A
parathyroid, pancreas, pituitary
-two of three involved for dx
19
Q
What are skin findings associated with MEN1 cancer syndrome?
A
angiofibromas, collagenomas, lipomas, CALs, confetti like lesions
20
Q
What can pituitary dysfunction cause in MEN1 cancer syndrome?
A
prolactinomas–> sexual dysfunction
21
Q
What percent of MEN2 is MEN2A or MEN2B?
A
70-80% MEN2A
20-30% MEN2B
22
Q
What is the risk for MTC in MEN2A\, MEN2B, FMTC?
A
95% in MEN2A in early adulthood
100% in FMTC in middle age
100% in MEN2B in early childhood
23
Q
What is the genetic cause of 95% of cases of MEN2B?
A
RET Met918Thr
24
Q
What is the Brazilian founder variant in TP53?
A
c.101G>A
p. Arg337 His
25
How is breast cancer characterized in LFS?
often ER and PR positive, and HER2 positive
26
When should TP53 variants identified on germline genetic testing be thought to be somatic variants?
if low allele fraction <40%
27
What is the lifetime risk of breast cancer with atypical ductal or lobular hyperplasia?
20-25% lifetime risk no fhx
up to 40% with fhx
28
What is the risk DCIS becomes invasive ?
up to 30%
higher chance with comedo
29
What type of ovarian cancer is BRCA usually associated with?
high grade serous
30
How do PARP inhibitors function?
BRCA cells still have functioning BER repair
PARP blocks BER repair --> cancer cells die
31
When is an oophorectomy recommended for individuals with pathogenic mutations in BRCA1 and BRCA2?
BRCA1: 35-40
BRCA2: 40-45
32
What type of colon polyp has the most malignant potential?
adenomatous
33
What type of APC variant is more likely to be pathogenic?
protein truncating variants
34
Where are APC variants that are most likely to cause attenuated FAP located?
5' or 3' end
35
What is the AJ APC founder mutation?
Ile1370Lys
36
What is the typical age of presentation of MUTYH related polyposis?
50s
37
What MMR genes have the greatest overall cancer risk?
MLH1 and MSH2
38
What AR condition can EPCAM cause?
congenital tufting enteropathy
intractable diarrhea of infancy, severe malabsorption due to intestinal epithelial dysplasia
39
How is Muir Torre syndrome characterized?
Lynch syndrome + sebaceous carcinomas and keratocanthomas
40
How is Turcot syndrome characterized?
multiple colorectal adenomas + primary brain tumors
APC + medulloblastoma
MMR + glioblastoma
41
When do the characteristic pigmented lesions of PJS appear?
after birth
42
How is Peutz Jeghers syndrome dx?
two or more of:
-PJS polyps
-fhx
-characteristic hyperpigmentation
43
What is the typical polyp type in juvenile polyposis syndrome?
hamartomatous or mixed
44
What other condition can be seen along with juvenile polyposis syndrome?
SMAD4 also causes HHT
45
How is type 1 VHL characterized?
HIGH hemangioblastoma
HIGH RCC
LOW Pheo
mutation types: deletions, nonsense, splice
46
How is type 2a VHL characterized?
HIGH hemangioblastoma
LOW RCC
HIGH Pheo
mutation types: missense, Tyr98His, Tyr112His
47
How is type 2b VHL characterized?
HIGH hemangioblastoma
HIGH RCC
HIGH Pheo
mutation types: partial deletions, nonsense, misssense
48
How is type 2c VHL characterized?
NO hemangioblastoma
NO RCC
HIGH Pheo
mutation types: missense, Ser80Leu, Val841, Leu188Val
49
What sub types of VHL do not have high risk for RCC?
type 2a: low
type 2c: none
50
What exons of the RET gene are associated with MEN2A, FMTC, and MEN2B?
exons 10-11: 2A
exon 13: 2A, FMTC
exons 14-16: 2B, FMTC
exon 16: 2B Met918 Thr
51
What is the penetrance of Birt Hogg Dube syndrome?
85%
52
What is the risk of RCC in BHD?
15-45%
53
What type of RCC is seen in hereditary leiomyomatosis renal cell carcinoma syndrome?
papillary type 2: fried egg appearance
also with uterine fibroids
54
What is the most common CHEK2 mutation?
1100del
55
What CHEK2 mutation is considered to be low penetrance?
I157T
56
What is the most aggressive type of renal cancer and what condition is this seen in ?
papillary type 2
HLRCC
57
What cancer syndrome is characterized by papillary type 1 RCC?
hereditary papillary RCC (MET)
58
What percent of RB is unilateral or bilaterla?
60% unilateral mean dx 24 months
40% bilateral mean dx 15 months
59
What is avoided in treatment of RB?
radiation avoided to minimize later cancer risks
60
What types of RB variants are considered to be lower penetrance?
inframe, missense, splice site, certain indels of exon 1 or promoter region
61
What is a common characterization of MAP associated CRC tumors?
KRAS somatic variant in 60-90%
10-25% of CRC with KRAS variant have MAP
62
What is the lifetime risk of CRC without surveillance for MAP?
80-90%
63
Where are hamartomatous polyps usually found in PJS?
mostly small intestine
64
What type of ovarian tumors are found in PJS?
mostly sex cord
65
What type of STK11 mutation is associated with a more severe phenotype?
premature stop codons
66
What gynecologic finding is found in individuals with HLRCC?
uterine fibroids, an cause irregular and heavy menses
67
How is RCC in HLRCC characterized?
papillary type 2
typically unilatera, solitary, aggressive with poor survival
onset often ~30
68
What can biallelic mutations in the gene that causes HLRCC cause?
FH gene
fumarate hydratase deficiency
69
What are skeletal findings associated with Nevoid BCC syndrome?
bifid ribs, vertebrael anomalies, pre or post axial polydactyly
70
What are additional cancer risks associated with Nevoid basal cell carcinoma syndrome?
cardiac fibroma- 2%
ovarian - 20%
medulloblastoma- 5% (higher with SUFU mutation)
71
Are lung or renal findings more prevalent in BHD?
pulmonary cysts in 70-80%
pneumothorax 25%
RCC in 19-35%
72
What tumor type is most common in MEN1?
parathyroid tumors- in 90% by age 20-25
hypercalcemia by age 50
73
What can cause sexual or menstrual dysfunction in MEN1 cancer syndrome?
pituitary tumors -> prolactinomia
74
How is MEN1 syndrome dx clinically?
-2 of main tumor types (parathryoid, pituiary, GEP)
OR
-1 main tumor type + 1 FDR
75
What is typically the first symptom in MEN1?
primary hyperparathyroidism
76
How is FMTC dx clinically?
4 or more cases in family without other MEN related cancers
77
How is medullary thyroid cancer characterized in FMTC?
presents at younger age and is more often associated with C cell hyperplasia
78
What are the highest cancer risks in PTEN syndrome?
85% breast
75% thyroid - benign or cancerous
28% endometrial
90% polyps- variable histology
35% RCC
79
How does H. pylori affect CDH1?
can induce promotor hypermethylation at CDH1
80
What causes hearing loss in VHL?
endolymphatic sac tumors
81
How is VHL dx clinically?
two or more characteristic lesions
OR one characteristic lesion + fhx
(endolymphatic sac tumor and pancreatic neuroendocrine tumor not used for dx)
82
What group affected by VHL is more likely to have CNS hemangioblastomas?
males with partial deletions
83
When do most adrenocortical carcinomas occur in LFS?
before the age of 5
84
How is LFS dx clinically?
all three of the following or a pathogenic variant in TP53:
-proband with sarcoma <45
-FDR with any cancer <45
either
--FDR or SDR with any cancer <45
--anyone with sarcoma at any age
85
What percent of individuals with hypo diploid acute lymphoblastic leukemia before 21 are affected by what cancer predisposition disorder?
50% with LFS
86
What is the Brazilian TP53 founder mutation?
p. Arg 337 His
87
What type of breast cancer is associated with LFS?
ductal, ER and PR + , HER2 amplification (triple positive)
88
What type of CNS tumor are most common in LFS?
glioblastoma and astrocytomas
89
What percent of individuals with XP have neurologic findings and what are they?
25%
microcephaly, diminished reflexes, progressive SNHL, progressive cognitive, ataxia
90
What pathway is affected in XP?
NER pathway
UV exposure --> cyclobutane dimers which cannot be repaired
91
Which cancers have a greater risk in BRCA1 vs BRCA2 associated HBOC?
BRCA1> BRCA2
breast 55-72% vs 45-69%
ovarian 39-44% vs 11-17%
BRCA1
92
How does the pathology of BRCA1 and BRCA2 tumors differ?
breast
BRCA1: higher grade, often triple negative
BRCA2: ER and PR +, 16% triple negative
BRCA2 prostate tumors are more aggressive
93
What is a reduced penetrance allele for BRCA1?
p.Arg1699Gln
intermediate risk
94
What LS gene carries the greatest CRC risk?
EPCAM 75%
then MLH1 (44-53%) and MSH2 (42-46%)
95
What MMR genes carry the greatest uterine cancer risk?
MSH2 (46%) MSH6 ( 41%)
96
What MMR gene carries the greatest ovarian cancer risk?
MSH2 (17%)
97
What MMR genes carry the greatest stomach and small bowel cancer risk?
MLH1 and MSH2
98
What MMR gene carries the greatest risk for bladder, prostate, and breast cancer?
MSH2
99
What percent of CRC has somatic BRAF mutations vs LS related CRC?
BRAF in 15% of CRC overall
only in 1.6% LS CRC
100
What is the role of the MMR pathway?
identifies and removes SNP mismatches or insertion or deletion loops
101
How is fertility affected in Bloom syndrome?
women- fertile with early menopause
men-infertile
102
What are cytogenetic findings of Bloom syndrome?
increased sister chromatid exchanges
increased quad radial configurations in cultured blood lymphocytes
chromatid gaps, breaks, and rearrangements
