Cancer Flashcards
1
Q
Tumor location in HNPCC vs. general population
A
HNPCC - usually right sided
General Population - usually left sided
2
Q
Inheritance pattern of PGL-1
A
Mutations in SDHD
AD inheritance
Tumors only develop if mutation is inherited paternally (Due to maternal genomic imprinting)
3
Q
Two reasons why IHC for MLH1 may reveal loss of staining
A
1) Germline mutation of MLH1
2) Somatic BRAF mutation (at codon 600, codint for valine) caused a somatic LOF in MLH1 (MLH1 promoter is methylated, turning off gene expression).
4
Q
Breast, colon, pancreas, stomach, ovary, sex cord tumor, Sertoli cell tumor, lung, small bowel, uterine
A
Peutz-Jegher syndrome associated cancers
5
Q
Amsterdam Criteria
A
3 or more affected people
2 or more generations
1 CRC must be by age 50 years
FAP must be excluded.
Amsterdam I: only CRC
Amsterdam II: others
6
Q
- Families that have a pattern of CRC that appears to be hereditary (only CRC and no other cancer types)
- Micro satellite stable and intact IHC
A
Familial Colon Cancer Syndrome X
7
Q
Screening for people with FAP
A
Polyp screening (starts at 10 years), thyroid cancer screening, hepatoblastoma screening, physical exam for extracolonic screening
8
Q
t(9;22)
A
CML - philadelphia chromosome, fusion gene of BCR-ABL (Chimeric protein) with enhanced tyrosine kinas activity
9
Q
Colon cancer, lobular breast, and gastric
A
Hereditary diffuse gastric cancer
10
Q
Colon, gastric, small bowel cancer
A
Juvenile polyposis syndrome
11
Q
CHRPE and desmoid tumors are _ in AFAP
A
rare (present in classic FAP)
12
Q
AFAP location of APC mutations
A
located at 5’ and 3’ ends
13
Q
Proximal polyps
A
AFAP
14
Q
CHRPE
A
Congenital hypertrophy of the retinal pigment epithelium (seen in FAP)
15
Q
Extracolonic features of FAP
A
small bowel polyps, gastric polyps, desmoid tumors, osteomas, dental abnormalities, CHRPE, benign cutaneous lesions (epidermoid cysts and fibromas), adrenal masses (7-13%) - most without endocrinopathy or hypertension
16
Q
Polyposis, CRC, small bowel, pancreatic adenocarcinomal, papillary thyroid carcinoma, hepatoblastoma, CNS (usually medulloblastoma), bile duct adenocarcinoma
A
FAP
17
Q
Ovary, Urinary tract cancer, stomach, biliary tract, endometrial, CRC
A
Lynch related cancers
18
Q
I1307K mutation
A
AJ common mutation - utility of testing is questionable - positive result will not change management. I1307K is a missense mutation creating a hypermutable area in APC (increased lifetime risk of CRC, NOT associated with FAP or AFAP)
- Level of risk same as first degree relative with CRC
19
Q
Medulloblastoma, multiple adenomatous polyps or polyposis,
A
Turcot syndrome (variant of FAP - no extracolonic addition features like CHRPE)
20
Q
Breast cancer, follicular thyroid cancer, uterine cancer
A
Cowden (PTEN)
21
Q
Breast, ovary, male breast, prostate, pancreatic, melanoma
A
BRCA2
22
Q
Breast, second primary breast, ovary. MAYBE colon, pancreas, and male breast
A
BRCA1
23
Q
Founder mutations of AJ for BRCA1/2
A
185delAG (BRCA1)
5382insC (BRCA1)
6174delT (BRCA2)
24
Q
Gene most likely to cause hereditary ovary cancer
A
BRCA1 (70%)
25
Gail model does not include
Does not include: other cancers (like ovary), second degree relatives, paternal history, age at cancer diagnoses in relatives
26
When is it inappropriate to use the Gail Model?
If a woman has previously had DCIS, LCIS, or a diagnosis of breast cancer, fam history of other cancers, 2nd degree relatives with cancer, paternal history, young age of diagnoses in relatives
27
Gail Model estimates
1) Absolute lifetime risk of breast cancer to 90 years of age
2) five year breast cancer risk
28
Factors included in Gail
1) Age
2) Age at menarche
3) Age at first live birth
4) number of FDR with breast cancer
5) ever had a breast biopsy
6) number of breast biopsies
7) Presence of atypical hyperplasia
8) race
29
Nephrectomies are performed when the tumors are
>3 cm
30
MET
proto-oncogene, causes hereditary papillary renal carcinoma
31
Claus model estimates
cumulative breast cancer risk based on family history alone
32
To effectively use a claus model table
"fudging" approximate the degree of genetic relationship (FDR or SDR) to a patient. Examples, no mother-maternal grandmother relationship - use mother-maternal aunt relationship.
33
FH gene
Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)
34
HLRCC
uterine leiomyomata (benign tumors containing smooth muscle), single or multiple cutaneous leomyoma, renal tumors (usually solitary) - often papillary and occasionally clear cell
35
CDH1
Hereditary Diffuse Gastric Cancer
36
BMPR1A and SMAD4
Juvenile polyposis syndrome (can also see PTEN). SMAD4 with HHT.
37
Juvenile polyposis with AVMs, mucocutaneous telangiectases, frequent nosebleeds, intracranial bleeds
SMAD4 - JPS/HHT syndrome
38
STK11
Peutz-Jeghers
39
CNS hemangioblastoma, retinal hemangioblastoma (may be the first manifestation), multiple renal cysts, pheochromocytomas, pancreas lesions and endolymphatic sac (ear) tumors, epididymal tumors
VHL
40
MUTYH
biallelic mutations - presents like AFAP, may have extracolonic features (CHRPE, osteomas)
41
90% of Lynch is caused by
mutations in MLH1 and MSH2
42
Proximal colon cancer
Lynch (AFAP also usually have more proximal placed polyps than regular FAP)
43
Jaw keratocyst
Gorlin syndrome
44
Falx calcification on skull x-ray, jaw keratocyst, two or more palmar or plantar pits, multipl basal cell carcinomas, medulloblastoma, congenital malformations
Gorlin Syndrome
45
PTCH1
Gorlin syndrome
46
De novo rate of APC
30%
47
Brain or CNS cancers
VHL - hemangioblastoma
NF - peripheral nerve sheath, optic glioma, astrocytoma
Gorlin - medulloblastoma
Turcot - variant of FAP, medulloblastoma
48
Pheochromocytomas
```
VHL
NF1
MEN2A
MEN2B
PGL1
PGL4
Carney Complex
```
49
Parathyroid, Pituitary, Gastro-entero-pancreatic, carcinoid, adrenocortical
MEN1 (PPP)
50
RET
causes MEN2
51
Oncogenes
RET, MET, MYC, RAS
52
SDHD
(PGL1) Pheo or PGL, no other manifestations
53
SDHC
(PGL3) PGL, no other manifestations
54
SDHB
(PGL4) Pheo or PGS, clear cell renal carcinoma
55
PGL2
Gene not known, PGL but no other manifestations
56
Symptoms of a pheo hypersecreting catecholamines:
- episodic sweating
- blood pressure elevation
- anxiety
- palpitation
- weight loss
57
Renal cancer
```
VHL
Hereditary Papillary Renal Carcinoma
BHD
HLRCC
Tuberous Sclerosis
SDHB (hereditary paraganglioma 4)
```
58
Breast cancer risk for Peutz Jeghers
54%
59
Trichelemmomas, papillomatous papules, lipomas
Cowden syndrome
60
Soft tissue skin tumors (epidermal cysts)
Gardner syndrome
61
Sebaceous carcinomas or adenomas, keratoacanthomas
Muir-Torre
62
Fibrofolliculomas
BHD
63
Cutaneous leiomyomata
HLRCC
64
Cutaneous schwannomas
schwannomatosis
65
Hypomelanotic macules, facial angiofibromas, shagreen patches, ungula fibromas
Tuberous Sclerosis
66
Eyelid and oral neuromas
MEN2B
67
Pits on palms or soles
NBCCS
68
Telangiectasias near surface of skin
Ataxia telangiectasia
69
Inherited cases vs. sporadic of Retinoblastomas
40% - inherited
| 60% - sporadic
70
Retinoblastoma in infants is associated with
a 400-fold increased risk for development of other cancers in adult life (much higher risk if child received radiotherapy)
Often develop mesenchymal tumors including osteogenic sarcomas, fibrosarcomas, and melanomas
71
t(8;14)
Burkitt's lymphoma, result of an apparently balanced t(8:14) chromosome translocation. Moves the MYC proto-oncogene to be placed downstream of a strong, constitutive promoter belonging to another gene
72
Proto-oncogenes
MET, RET, MYC
73
VHL subtype 2C
Only increased risk for pheos (not hemangioblastoma or RCC)
74
Percentage of MTC that is hereditary vs. sporadic
25% = hereditary
75% = sporadic
(10% of all thyroid cancer is medullary)
75
Hamartomatous polyps
PJS and Cowden
76
Adenomatous polyps
FAP, MYH polyposis, PJS, JPS, Hereditary mixed polyposis
77
Juvenile polyps
JPS (atypical ones seen in Hereditary mixed polyposis)
78
Hereditary Mixed polyposis types of polyps
Atypical juvenile, adenomatous, benign colonic lesions, metaplastic, inflammatory
79
GI tract - location of polyps
PJS, JPS, Cowden
80
Most polyps in small intestine
PJS
81
Stomach to rectum an dGI Tract
JPS
82
Colon = location of polyps
FAP, MUTYH, Hereditary mixed polyposis
83
Clear cell renal cancer
VHL (bilateral/multifocal) or HLRCC (solitary)
84
Papillary renal cancer
Hereditary papillary (bilateral/multifocal), Type II papillary in HLRCC (solitary)
85
Chromophobe, hybride chromophobe/oncocytoma
BHD (bilateral/multifocal)
86
Malignant peripheral nerve sheath, plexiform neurofibroma, optic glioma
NF1
87
Schwannoma, meningioma, spinal cord glioma
NF2
88
Schwannoma
Schwannomatosis
89
Plexiform neruofibroma, optic glioma, brain stem or cerebral glioma, malignant peripheral nerve sheath tumors, pheochromocytoma
NF1
90
Renal cysts or angiomyolipomas, retinal nodular hamartomas, subenpendymal nodules, cortical tubers, giant cell astrocytomas, lymphangiomyomatosis
Tuberous Sclerosis
91
c-cell hyperplasia
RET mutations
92
MTC, pheos, hyperparathyroidism
MEN2B
93
Sarcoma, brain tumor, breast CA, leukemia, adrenocoritcal carcinoma, choroid plexus tumor
Li-Fraumeni
94
Genotype-phenotype correlations with MSH6 and PMS2
MSH6: ~30% less risk for colon cancer, predominance of endometrial cancer
PMS2 heterozygote: low penetrance
PMS2 homozygotes: very early onset CRC, duodenal CA, leukemia, lymphoma, childhood brain tumors, cafe au lait spots
95
Sarcoma
Tumor arises in mesenchymal tissue such as bone, muscle, connective tissue, or nervous system tissue
96
Carcinoma
tumor arises in epithelial tissue, such as the cells lining the intestine, bronchi, or mammary ducts
97
Hematopoietic or lymphoid neoplasm
Neoplasm that spreads throughout the bone marrow, lymphatic system, and peripheral blood
98
Oncogene
Mutant gene of a proto-oncogene that facilitates malignant transformation by stimulating proliferation or inhibitin apoptosis.
"Activation" is the transformation from proto-oncogene to oncogene
Activation typically occurs in somatic cells
Effect at cellular level = dominant
99
Gatekeeper tumor-suppressor gene
Controls cell growth and blocks tumor dvelopment by regulating the transition of cells through checkpoints in the cell cycle or by promoting programmed cell death.
Directly controls cell division and survival
LOF mutations lead to uncontrolled cell accumulation
Examples: RB1, TP53
100
Caretaker Tumor Suppressor
Protects the integrity of the genome
LOF mutations permits mutations to accumulate in oncogenes and gatekeeper genes, which go on to initiate and promote cancer development (indirectly allows cancer formation)
Example: MLH1, MSH2
101
Tumorigenesis
1) Normal tissue cell receive proliferative signals
2) Normal tissue becomes a pre-cancerous lesion
3) Early cancer forms
4) Malignant Cancer
102
DCIS
NO ABILITY TO METASTASIZE
About 30% chance of invasive breast cancer if left untreated
103
Shagreen patches
Tuberous Sclerosis Complex
104
TSC1, TSC2
Tuberous Sclerosis Complex
105
PRKAR1A
Carney complex
106
Myxomas, thyroid carcinoma, sertoli cell tumors, breast, endocrine, spotty skin pigmentations, mucosal pigmentation, psammomatous melanotic schwannoma, blue nevi
Carney complex
107
Bilateral acoustic Schwannoma
NF2
108
Macrocephaly, polyposis, lipomas, pigmented macules of the glans penis
Bannayan-Riley-Ruvalcaba (PTEN)
109
CT nevi, disproportional overgrowth, dysregulated adipose tissue, vascular malformation, risk of ovarian or parotid tumor in 2nd decade
Proteus syndrome (PTEN)
110
Mucocutaneous facial and oral papules, gingival cobblestonine, acral keratosis, dystrophic and adenomatous multinodular goiter, GI polyps, adenosis and fibrocystic breast lesions, macrocephaly, dolichocephaly, lipomas, GU anomalies, breast, thyroid, and endometrial cancer
Cowden syndrome (PTEN)
111
PITCH1 and SUFU
Nevoid Basal Cell Carcinoma Syndrome (Gorlin)
112
Paragangliomas
tumors of the sympathetic nervous system (commonly head, neck, thorax, abdomen).
97% are benign and will not metastasize
113
Carney Triad
1) Gastric leiomyosarcoma
2) pulmonary chondroma
3) adrenal adenoma
114
PRKAR1A
Carney complex
115
FLCN
BHD
116
"fried egg" appearance of nuclei
papillary type II RCC - found in HLRCC
117
CDKN2A mutations
Hereditary melanoma (20-40% of hereditary cases)
118
CDK4
Hereditary melanoma
119
Malignant melanoma in one or more FDR or SDR
>50 nevi (some atypical)
Familial Atypical Multiple Mole Melanoma (FAMMM)
Caused by CDKN2A or CKD4
120
Extreme photosensitivity, premature skin aging
Xeroderma Pigmentosum (AR)
121
Immunodeficiency, progressive cerebellar ataxia, enhanced sensitivity to radiation, leukemia, lymphoma
Ataxia Telangiectasia
122
Hyperpigmentation, CAL, thumb anomalies, other skeletal anomalies, small stature, low birth weight, microcephaly, renal anomalies, hypogenitalism, strabismus, microophthalmia, hyperreflexia, ID, ear anomalies and/or deafness, CHD
Fanconi Anemia
123
Fanconi Genes (besides FANC ones)
BRCA2, BRIP1, PALB2, RAD51C, SLX4
124
Retinoblastoma
RB1 mutations, AD inheritance, classic two hit hypothesis
125
Pinealoma or primitive neuroectodermal tumors of the brain, osteosarcomas, soft tissue sarcomas, melanoma
Retinoblastoma related tumors
126
FWT1 and FWT2
Wilms tumor
127
Conditions associated with Wilms tumors
FWT1, FWT2, BWS, Isolated hemihyperplasia, WAGR, Denys Drash, Li-Fraumeni
128
Constitutional mismatch repair deficiency
Biallelic mutations in genes that cause Lynch syndrome (MLH1, MSH2, MSH6, and PMS2)
MLH1/MSH2 - earlier onset, higher hematological prevalence
MSH6/PMS2 - later (~9) onset, higher brain/LS tumor prevalence
129
MET
Papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers
130
Absence of MLH1 and PMS2 could be:
MLH1 germline mutation or MLH1 promoter hypermethylation (rule out through BRAF testing)
131
Absence of just PMS2 could be
MLH1 germline mutation or PMS2 germline mutation
132
Absence of MSH2 and MSH6 could be
MSH2 germline mutation or EPCAM germline mutation (EPCAM is just upstream of MSH2, 3' EPCAM deletions can lead to absence of MSH2 expression)
133
Absence of just MSH6 could be
MSH6 germline mutation
134
Choroid Plexus Carcinoma
Li-Fraumeni
