Cancer Midterm Flashcards
(240 cards)
1
Q
Most common hereditary cancer syndrome
A
Lynch
2
Q
Ascending colon is on the [ ] side
A
right
3
Q
What % of CRC is hereditary?
A
5-10%
4
Q
What % of CRC is familial?
A
30% (high compared to other cancers)
5
Q
What are possible reasons for familial cancers?
A
Environment, low/moderate penetrance alleles, polygenic mechanism, chance
6
Q
General pop lifetime risk for CRC?
A
5%
7
Q
Sporadic cancer
A
No known inherited risk component in the cancer etiology. Not related to other cancers in the family.
8
Q
Hereditary cancers
A
single gene, genetic predisposition, high penetrance, limited environmental role
9
Q
Increased risk factors for CRC
A
male, obesity, diabetes, alcohol, tobacco, red meat, processed meat, bbq meat, IBD, family hx
10
Q
Decreased risk factors for CRC
A
physical activity, fiber, folate, calcium, aspirin
11
Q
What cancer seems to be highly tied to diet?
A
CRC
12
Q
Increased risk of CRC with affected first degree relative
A
2-3x (10-15%)
13
Q
Polyposis syndromes
A
FAP, MAP, Peutz-Jegher’s Syndrome, Juvenile Polyposis, Hyperplastic Polyposis, Hereditary Mixed Polyposis
14
Q
Non polyposis CRC
A
Lynch
15
Q
Lynch CRC and endometrial onset
A
40-45. Early, but variable
16
Q
Other cancers related to Lynch
A
urinary tract, ovary, stomach, small bowel, hepatobiliary, brain, sebaceous skin
17
Q
Lynch gene classification
A
mismatch repair genes (MMRs)
18
Q
Lynch genes
A
MLH1, MSH2, MSH6, PMS2
19
Q
Most common lynch mutations are in
A
MLH1 and MSH2
20
Q
What are the two “strong” lynch genes?
A
MLH1 and MSH2
21
Q
MLH1 dimerizes with?
A
PMS2
22
Q
MSH2 dimerizes with?
A
MSH6
23
Q
What does an EPCAM mutation do?
A
3’ deletion shuts off MSH2 via epigenetic silencing
24
Q
risk of colon cancer with Lynch
A
50-80% (lower for MSH6 and PMS2, but NCCN groups them all together)
25
most common endometrial cancer
endometriod, which is an adenocarcinoma
26
Lynch ovarian cancer pathology
epithelial forms other than serous
27
why do tumor testing in Lynch?
establish probability of Lynch, identify genes (without expensive genetic tests), targeted therapy
28
MSI
Microsatellite instability. 90% of Lynch tumors show this
29
Is abnormal IHC a diagnosis of Lynch syndrome?
No. Lynch defined by germline mutation of 5 lynch genes
30
What could mimic Lynch?
acquired hypermethylation of MLH1 promoter (shuts off MLH1. Not inherited. Note that this does not rule out Lynch 100%).
31
BRAF
A mutation that causes cell proliferation in many cancers. Thought to be rare in Lynch, so used to rule out Lynch
32
Lynch gene testing criteria
Amsterdam (very strict). Bethesda (less strict, still misses lots of families)
33
Muir Torre
Colorectal neoplasia and sebaceous skin tumors. Mostly due to MSH2
34
Turcot
Colorectal neoplasia and CNS tumors. Could be APC or MMR genes
35
Lynch management
C'spy q 1-2 y starting at 20-25. Endometrial screening? (controversial)
36
Cancer risk reduction in Lynch
Colectomy, hysterectomy, salpingo-oopherectomy
37
MSI high tumor tx
Higher survivorship, don't respond as well to standard chemo, but promising findings for immunotherapy
38
Lynch preventative drugs
oral contraceptives for ovarian and endometrial cancer. High doses of aspirin for CRC
39
Cancer death stats
Almost 1/4 of deaths in US, exceeded only by heart disease
40
Cancer lifetime risk
1 in 2 men and 1 in 3 women
41
Most common cancer sites
prostate/breast, lung, colorectal (in order)
42
Site associated with highest cancer deaths
lung
43
Incidence
number of newly diagnosed cases in a particular time period
44
prevalence
total number of cases (includes survivors)
45
mortality rate
frequency of occurrence of death in a defined population in a defined interval
46
SEER
collects information on incidence, prevalence and survival from specific geographic areas representing 28 percent of the US population and compiles reports on all of these plus cancer mortality for the entire country.
47
what is cancer?
diseases in which abnormal cells divide without control, leading to a mass or tumor that can invade other tissues.
48
What is a tumor?
mass of abnormal cells
49
benign tumors
no not have ability to invade other tissues but may cause symptoms due to position
50
malignant tumors
capable of invading other tissues
51
carcinoma
cancer that begins in epithelial tissue (skin, tissues that line or cover internal organs). Think tubes
52
sarcoma
cancer that begins in connective and supporting tissues (bone, cartilage, fat, muscle, blood vessels)
53
Hematopoietic and lymphoid
spread throughout the blood, lymphatic system or bone marrow (leukemia, lymphoma)
54
Melanoma
arise in pigmented ectodermal cells
55
Stages of carcinogenesis
initiation, promotion, tumor progression
56
Initiation
mutation in single cell. Reversible (can be inherited, but most often is somatic)
57
Promotion
further errors in cell division or exposure to promoting agents such as hormones promote growth. Precancerous, possibly still reversible
58
Progression
Irreversible now. Mutations accumulate b/c rapid cell division. Eventually tumor is fully malignant cells, some with metastatic capabilities.
59
Metastasis
Malignant cells undergo further changes to become metastatic. Cell must be able to separate from the primary tumor, enter into circulatory or lymphatic system, escape the immune system, enter the target organ, attach to the surface of the new tissue site, proliferate cells to create a new tumor, provide nourishment for the new mass.
60
Common metastasis sites
Lung, liver, bone, CNS
61
Tumor grade
How abnormal are the cells? How different from the surrounding cells?
62
Low grade tumor
Well differentiated- only minor differences from surrounding cells
63
High grade tumor
Moderate or poor differentiation- does not resemble surrounding cells. Nomenclature can differ based on organ.
64
clinical stage
location. degree of metastases. I-IV
65
Staging TNM system
Used for solid tumors
T: size/appearance
N: lymph node involvement
M: extent of metastases
66
carcinoma in situ
early form of carcinoma defined by the absence of invasion of surrounding tissues. "Stage 0"
67
cause of cancer
mutations in genes that regulate cell growth and cell death
68
Proto-oncogene
gene involved in some aspect of cell proliferation. May become activated by gain-of-function mutation to become an oncogene.
69
Oncogene
dominantly acting gene responsible for tumor formation. ONE mutation enough to lead to cancer.
70
tumor suppressor genes
Encode proteins that negatively regulate growth of cells (i.e. stop growth of damaged cells). Inactivation of BOTH copies leads to cancer development. Dominant in terms of inheritance, but recessive in terms of molecular mechanism. Two hit hypothesis.
71
Knudson's two hit hypothesis explains
early onset, multiple primaries, dominant inheritance with incomplete penetrance
72
mismatch repair genes
inactivation of genes involved in DNA repair leads to accumulation of DNA errors in cell. If these occur in proto-oncogenes or tumor suppressor genes, could result in tumor formation
73
How much of cancer is hereditary?
About 10%
74
Familial/multifactorial cancer characteristics
combo of genetic and environmental, number of cancers in family more than expected and/or younger ages
75
Hereditary cancer characteristics
Most cancers in family due to single genetic factor. Early onset. Same or related cancers. Multiple primaries. Rare cancers. Associated anomalies. Known ethnic risk.
76
colorectal polyps
overgrowth of epithelial cells
77
3 morphologies of polyps
pedunculated (mushroom), sessile (fingers), flat
78
which polyps have highest cancer risk?
adenomas
79
adenomatous polyp histology
tubular (often pedunculated, with tubes)
villous (often sessile, with branches)
tubulovillous (combination of both)
80
which adenomas have highest risk of becoming cancer?
Villous
81
hamartomatous polyps
mix of tissues, low malignant potential, relatively common. Associated with P-J syndrome, Cowden, and juvenile polyposis syndrome.
82
hyperplastic polyps
benign lesions (exception: sessile serrated). Increased number of normal, organized cells. Still usually removed to confirm normalcy.
83
sessile serrated
rare, precancerous hyperplastic polyp.
84
inflammatory polyps
pseudopolyps. Seen with IBD. not malignant
85
familial adenomatous polyposis mutations
APC mutations. 1/3 de novo
86
FAP cancer risk and onset
100s to 1000s of adenomatous polyps. Mean polyposis onset is 16. Mean CRC onset is 39. 100% lifetime risk of cancer. Colectomy required.
87
Other findings in FAP
desmoid tumors, osteomas, soft tissue tumors, CHRPE, dental abnormalities
88
Four "forms" of FAP
FAP, AFAP, Gardner, Turcot
89
AFAP
Average of 30 polyps, later onset of CRC, lifetime CRC risk is 80-100%, no CHRPE, some different mutations in APC
90
Gardner syndrome
FAP plus soft tissue tumors and osteomas
91
Turcot
CRC and CNS tumors (usually medulloblastoma)
92
I1307K mutation
In APC. Does not mean you have FAP. Common in AJ pop. Slight increase in CRC risk. Start c'spy at 40, every 5 yrs
93
MUTYH-associated polyposis
MAP. Autosomal recessive. Similar to FAP/AFAP phenotype. 80% CRC risk
94
MUTYH gene
DNA repair of oxidative damage.
95
Juvenile Polyposis Syndrome polyps and cancer risk
Most common hamartomatous polyp syndrome. Most polyps benign. Polyps vary significantly, even in same family. Risk of GI cancers 9-50%.
96
JPS gene(s)
BMPR1A, SMAD4
97
Cancers associated with Cowden
Breast, endometrial, thyroid, kidney, colorectal (9%)
98
Cowden syndrome associated findings
Lhermitte Duclos, macrocephaly, penis pigmentation, mucocutaneous lesions, autism, ID, lipomas
99
Peutz-Jeghers gene
STK11
100
Peutz-Jeghers manifestations
mucocutaneous hyperpigmentation of mouth, face, fingers, genitals. Hamartomatous polyps of GI tract. GI, CRC, and breast cancers. Intussusception.
101
Hereditary Mixed Polyposis Syndrome
Mixed polyp types, usually not explained by genetic testing
102
Serrated Polyposis syndrome
highly variable presentation, increased risk of early onset CRC, no known genetic cause
103
NCCN and ACS consider a woman at increased risk of breast cancer if
1) she has a history of breast cancer
| 2) she is at 20% or greater lifetime risk of developing breast cancer based on modeling (largely dependent on family hx)
104
breast cancer screening recommendations for high risk women
annual mammo and MRI, alternating every 6 mo. MRI at 25, mammo at 30. (or 10 years before youngest family member?). Breast awareness. Consider risk-reducing options.
105
relative risk
(incidence in those with the risk factor) / (incidence in those without the risk factor)
106
cumulative risk
risk by a certain timepoint. Ex. lifetime risk
107
Age related penetrance
usually the chance of developing cancer in a certain age interval. Like, if you don't have cancer by 30, what's the chance you'll develop it by 40.
108
Gail model characteristics
for breast cancer. very little family history used. some hormonal hx
109
Claus model characteristics
for breast cancer. uses family history. no hormonal or pathology hx
110
risk model that works for people WITH breast cancer
BRCAPro. Estimates prob of having a BRCA mutation and for developing breast and some other cancers.
111
boadicea risk model
prob for BRCA mutation and breast cancer. UK pop. Includes lots of fam hx, tumor path, and prior genetic testing
112
Tyrer-Cuzick model
hereditary, hormonal, and path factors. Used often in PRS. Tends to overestimate risk.
113
Polygenic risk score
A liklihood ratio is created from various SNPs. Multiply baseline risk by this ratio. Idea is that any small number of tiny-risk SNPs won't change risk/management, but combination of 100s or 1000s might.
114
polygenic risk score output
odds ratio, which must be converted to absolute or cumulative risk or something like that that is useful in clinic
115
odds ratio
the odds of A in the presence of B and the odds of A without the presence of B.
116
in situ breast cancers
"stage 0." Some people call these precancers. Others don't. DCIS is intraductal. treated with lumpectomy and radiation. LCIS is not a cancer. Lobular. Not treated, just watched.
117
most common invasive breast cancer
IDC
118
breast cancer path markers
Estrogen, progesterone, Her2
119
BRCA is what type of gene?
tumor suppressor. repairs damaged DNA.
120
Features of BRCA mutation
early onset cancer, multiple cases of BC, ovarian cancer, breast and ovarian cancer in same woman, bilateral BC, male BC, AJ heritage, triple negative, prostate/melanoma/pancreatic cancers
121
BRCA1 lifetime risks
For women: 50-85% BC, 3%/year second primary BC, 30-54% ovarian
Male: 1% BC (10x gen pop), prostate increased
122
BRCA1 lifetime risks
For women: 50-85% BC, 3%/year second primary BC = 40-6-%, 30-54% ovarian
Male: 1% BC (10x gen pop), prostate increased
123
BRCA2 lifetime risks
For women: 56-85% BC, 20-30% ovarian cancer
| Men: 6-8% BC, prostate increased
124
Gen pop BC lifetime risk
12%
125
Gen pop ovarian lifetime risk
1.5%
126
BRCA1 BC path
often ER/PR -
127
BRCA2 BC path
often ER/PR +
128
BRCA Ovarian path
papillary serous. Prognosis better than for sporadic cancer. Fallopian tube cancer more common.
129
Breast cancer high risk surveillance for men
breast self exams at 35, clinical breast exams every 6-12 months. Prostate cancer surveillance at 40 instead of 50
130
risk reduction in BRCA women with mastectomy
>90%
131
tamoxifen mechanism
blocks hormone receptors, so best with BRCA2
132
chemoprevention for ovarian cancer
5 years of oral contraceptives. Best in 20s and 30s. 50% risk reduction in general pop. 60% risk reduction in BRCA1/2 positive women
133
surveillance for ovarian cancer
no reliable, standard methods. Can do ultrasound and blood tests.
134
risk reducing oophorectomy
reduces risk for ovarian cancer by 90% (peritoneal carcinomatosis still possible). 17% of time, cancer is found already when ovaries are removed.
reduces risk for breast cancer by 50% in premenopausal women with BRCA1/2 mutations (because of hormones)
135
Melanoma associated with
BRCA2 mutations
136
true negative
negative for known family mutation
137
When was BRCA identified?
1 in 1994, 2 in 1995
138
Percent of breast cancer that's hereditary
10%
139
Percent of hereditary breast cancer due to BRCA
up to 50%
140
Percent of hereditary breast cancer due to known genes other than BRCA
up to 30%
141
most likely path for BRCA1 BC
triple negative
142
high risk breast cancer genes
BRCA1, BRCA2, CDH1, PTEN, TP53
143
moderate risk breast cancer genes
ATM, CHEK2, PALB2, NF1
144
cancers associated with cowden
breast (up to 85%), thyroid (10%), endometrial (up to 30%), and benign hamartomatous growths of skin, colon, thyroid, etc.
145
clinical features of cowden
autism, intellectual disability, macrocephaly, lipomas, fibromas (lumps and bumps),
146
pathognomonic criteria for cowden
Lhermitte Duclos. >3 Trichilemmomas (benign tumor of face/hair line)
147
Cowden gene(s)
PTEN (30-35%), KLLN (30%), SDHX (?10%). Usually a clinical dx
148
cowden management
annual mammo and MRI at 30-35 or 5-10 before earliest relative. Consider RRBM. Consider hysterectomy after childbearing. Annual thyroid u/s starting at 18, c'spy at 35, every 5 yrs, annual derm exam, consider renal u/s at 40
149
Li-Fraumeni gene
P53. Auto dom. Checkpoint gene
150
Li-Fraumeni lifetime cancer risk
women: 90%
men: 70%
50% risk by age 30
early onset, multiple primaries
151
Li-Fraumeni core cancers
breast (onset in 20s, +/+/+)
sarcoma (soft tissue, bone, mean age 15)
brain (choroid plexus tumors and others)
adenocortical carcinoma (mean age 4, hallmark)
152
Li-Fraumeni criteria
classic (strict) and Chompret
153
Li-Fraumeni management
```
since Malkin 2011 extensive screening recommended. Early tumor detection improves survivorship.
Annual mammo/MRI at 20
Consider RRBM
Brain MRI yearly
abdominal u/s 3-4 months
rapid whole body MRI yearly
physical exam 3-4 months
c'spy at 25, q 2 years
blood tests q 3-4 months
derm exam yearly
```
154
CHEK2 role
cell cycle control and apoptosis
155
CHEK2 cancer risks
2-3x risk for BC. Consider MRI and tamoxifen. Increased risk of colon, prostate, thyroid. Mutation doesn't always track with cancers in the family.
156
ATM
Autosomal recessive Ataxia Telangiectasia. Carriers have a 20-45% risk of BC. Carrier frequency is 1%
157
PALB2
Partner and Localizer of BRCA2. BC risk 17-58%. 40% are triple negative
158
Average risk mammo recs
Depending on organization: q 1-2 yrs starting between 40 and 50
159
Lynch tumor characteristics
MSI high, IHC absence, high mutation tumor burden
160
MEN1 gene
Menin
161
MEN1 cancers
Pancreatic cancer: Islet cell/ neuroendocrine
162
MEN1 noncancer
```
Parathyroid adenoma
Pituitary adenomas
Adrenocortical tumors
Hypercortisolism
Hyperaldosteronism
Carcinoid tumors
Angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, leiomyomas
Paragangliomas
```
163
MEN1 surveillance
Annual prolactin, PTH, calcium testing beginning btw age 5-10
Head MRI every 3-5 yr
Abdominal MRI or CT every 3-5 yr
164
VHL cancer
Renal clear cell carcinoma (40% lifetime risk)
165
VHL noncancer
```
Pheochromocytoma
Hemangioblastomas
Endolymphatic sac tumors
Vision loss (retina heman.)
Anxiety, heart palpitations, high blood press
```
166
VHL Surveillance
```
Annual opthalmology by age 5
Annual blood pressure and urinary catecolemine metabolites by age 5
Annual abnominal US by age 16
Audiological Exam
Avoid tobacco
```
167
MEN2 gene
RET
168
MEN2 Cancer
Medullary thyroid cancer- commonly papillary path
169
MEN2 noncancer
Pheochromocytoma
Parathyroid adenoma/hyperplasia
Paragangliomas
170
MEN2 Surveillance
Determine age to remove thyroid by risk level (A-D system)
171
MEN2 subtypes
FMTC
Thyroid cancer only, by middle age
MEN 2A
Pheo, parathyroid adenoma, MTC in early adulthood
MEN 2B
Pheo, mucosal neuromas, MTC in early childhood
172
Pheos produce?
Catecholamines: epinephrine, norepinephrine, dopamine
173
Manifestation of hyperpapathyriodism?
Hypercalcemia
174
Biochemical screen for thyroid?
calcitonin
175
Hereditary Paraganglioma and Pheochromocytoma (HPGL/PCC) genes
SDH genes- part of electron transfer in mt membrane
176
Hereditary diffuse gastric cancer gene
CDH1
177
CDH1 cancers
Gastric cancer (50-80% lifetime)
Lobular breast cancer (40-50% lifetime)
Possibly CRC
178
CDH1 surveillance
Gastric cancer screening not very effective. RR gastrectomy recommended between age 18 and 40.
Annual breast MRI and mammo start at 30
179
RB1 surveillance
Exam under anesthesia every 4 weeks until age 1, less frequently until age 3, every 3-6 months until 7, every 1-2 years for life
180
RB unilateral vs bilateral
60% unilateral (but 15% of these have germline variant)
| 40% bilateral
181
RB1 secondary malignancies
soft tissue sarcomas, osteosarcomas, brain tumors, melanomas, Hodgkin’s, breast, lung, leiomyosarcoma (substantially increased with rx)
182
bone marrow failure
when bone marrow does not make enough healthy blood cells for body’s needs
183
Aplastic anemia
quantity issue- shortage of blood cells
184
Myelodysplastic
quality issue - abnormal blood cells
185
Fanconi Anemia features
Short stature, thumb abnormalities, small facial features, CALs
186
Fanconi Anemia Dx
DEB breakage studies (will show defective repair mechanism)
187
Dyskeratosis Congenita features
dysplastic nails, lacy skin on chest, oral leukoplakia
188
Dyskeratosis Congenita Dx
telomere length test
189
Prostate cancer genes
BRCA2, HOXB13, Lynch genes
190
Fanconi Anemia cancers
AML, head and neck squamous cell carcinomas
191
Constitutional Mismatch Repair Deficiency cancers
Young hematologic malignancies, brain cancers
192
Normal tissue staining in CMMR-D?
Absent staining in normal tissue, not just tumor (which is what we would see in Lynch)
193
DICER1
childhood lung cysts. Pleuropulmonary blastoma, ovarian sex cord tumors, cystic nephroma
194
paraganglioma
neuroendocrine tumor impacting sympathetic nervous system (fight/flight/homeostasis)
195
Lynch other cancers
"Endometrial: 25-60%
Gastric: 6 -13%
Ovarian: 5-10%"
196
FAP other cancers
GI, thyroid, pancreas, hepatoblastoma
197
FAP de novo rate
20-33% de novo
198
MAP carriers
"1-2% of pop are carriers
Carriers at some increased risk of CRC
Start c'spy at 40 if FHx CRC"
199
PJS cancers
```
Breast: 50%
CRC 40%
Pancreatic: 10-35%
Stomach: 30%
Ovary: 20%
Others: lung, small intestine, cervix, uterus
```
200
What condition has endometrial but not ovarian cancer?
Cowden
201
Prostate cancer genes
HOXB13, Lynch, HBOC, some moderate breast genes
202
Pancreatic genes/syndromes
FAP, FAMM, PJS, HBOC, PALB2, MEN1, Lynch, NF1, JPS, VHL, Li-Fraumeni
203
CDH1 cancers
40-50% lifetime risk of breast cancer, primarily lobular. Gastric: 50-80%
204
VHL features
"Renal clear cell carcinoma- 40% lifetime risk
Hemangioblastomas- CNS, retina
Pheos- norepinephorin
Endolymphatic sac tumors- hearing loss, vertigo
Pancreatic neuroendocrine tumors (PNETs)
Various cysts"
205
MEN1 features
"Parathyroid- Hyperparathyroidism -> hypercalcemia (lethargy, depression, confusion, nausea, kidney stones, bone fractures (90% by 25y)
Pituitary- prolactinomas, adenomas (10-60%)
Pancreas- islet cell (aka neuroendocrine) cancer (30-75%)
Carcinoid tumors
Adrenocortical tumors
Various lumps, bumps, tumors
206
RET gene
"Oncogene
For MEN2: GoF mutations, all missense
Genotype-phenotype well established (subtypes)
For Hirschsprung: LoF
207
FMTC
Medullary Thyroid Cancer (MTC) only, 100% by middle age
208
MEN2a
Pheo 50% (metanepherine)
Parathyroid adenoma/ hyperplasia 20-30%
MTC early adulthood 95%
209
MEN2b
```
Pheo 50% (metanepherine)
Mucosal neuromas
MTC in early childhood 100%
Ganglioneuromas in GI
Marfanoid
```
210
Hereditary Paraganglioma and Pheochromocytoma
"Renal clear cell carcinoma
| Papillary thyroid carcinoma"
211
Fanconi Anemia molecular info
"Crosslink repair genes
| Note biallelic BRCA2, PALB2, BRIP1, RAD51C are causes"
212
Fanconi Anemia features
"AML: 10-30%
| Macrocytosis, increased HbF, cytopenia, progressive BMF, aplastic anemia, may also develop myelodysplastic"
213
Fanconi Anemia dx
Chromosome breakage studies (DEB)
214
Dyskeratosis Congenita genes
DKC1 (X-linked), TERT, TERC
215
Dyskeratosis Congenita desc
"85% risk of bone marrow failure (aplastic anemia), MDS, AML
Classic triad: dysplastic nails, lacy pigmentation on chest/neck, oral leukoplakia
Pulmonary fibrosis"
Increased risk head/neck/genital squamous cell carcinomas
216
Dyskeratosis Congenita dx
Telomere length study- flow FISH
217
Birt Hogg Dube syndrome (BHD) gene
FLCN
218
Birt Hogg Dube syndrome (BHD) features
"90% of pt with lung blebs, which can cause spontaneous pneumothorax
30% of pts with chromophobe renal cancer
Most have fibrofolliculomas
219
Hereditary Leiomyotosis Renal Cell Carcinoma (HLRCC) gene
FH
220
Hereditary Leiomyotosis Renal Cell Carcinoma (HLRCC) desc
Fibroids, typically requiring early hyst
| Renal cell carcinoma- papillary type II (aggressive)
221
Hereditary Papillary Renal gene
MET (Proto-oncogene)
222
Hereditary Papillary Renal desc
"Renal cell carcinoma- papillary type I
| Onset typ. middle age"
223
DICER1 Syndrome desc.
"Cancerous: pleuropulmonary blastoma (childhood)
| Typically benign: cystic nephroma (childhood), Sertoli-Leydig cell tumors (young women), goiter"
224
Tuberous Sclerosis gene
TSC1, TSC2
225
Tuberous Sclerosis inher and molecular
AD, "70% sporadic, most of which are TSC2
30% familial, evenly split between TSC1/2
(TSC2 next to PKD1)"
226
Tuberous Sclerosis desc.
"Skin - hypomelanotic macules, facial angiofibromas, shagreen patches/collengenomas, ungual fibromas
Brain - cortical tubers, subependymal nodules, giant cell astrocytomas (SEGAs), seizures, learning differences, variable ID
Renal- angiomyolipomas, cysts
Cardiac- rhabdomyoma (prenatally, resolve in childhood)
Lung- lymphangiomyomatosis (LAM) – (females)"
227
Retinoblastoma features
Eye cancer, sometimes brain (pineal) cancer
228
Xeroderma pigmentosum inher
AR
229
Xeroderma pigmentosum features
"Basal cell carcinoma, squamous cell carcinoma
Melanoma
Ocular cancer
Neurologic (25% of cases): microcephaly, hearing loss, cognitive impairment, ataxia, seizure"
230
Familial Atypical Multiple Mole Melanoma (FAMMM) genes
CDKN2A, CDK4
231
Familial Atypical Multiple Mole Melanoma (FAMMM) desc
"Melanoma
Pancreatic cancer
Nerve sheath tumors"
232
Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) gene
PTCH1, SUFU
233
Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) desc.
"Basal cell carcinomas
>5 in lifetime
Early calcification of falx (x-ray skull <20y)
Jaw keratocysts (PTCH1)
palmar/plantar pits
Ovarian fibromas (not cancer)
Medulloblastoma (ped. brain cancer), mostly SUFU mutations"
234
Ataxia Telangiectasia
```
"Increased risk for leukemia and lymphoma
Immunodeficiency
Cerebellar ataxia starting around 1-4y
“Blood shot” eyes
Sensitivity to radiation"
```
235
Rare recessive cancer syndromes
AT, CMMR, NBS, Bloom, XP
236
Wilms Tumor genes and syndromes
FWT1, FWT2 and others, Also: overgrowth syndromes, WAGR, Denys Drash, Li-Fraumeni, Bloom
237
CMMR gene
MLH1, MSH2, MSH6, PMS2
238
CMMR desc
"Pediatric hematological malignancies
Pediatric brain tumors
Early onset CRC
CALMs"
239
Bloom gene
BLM
240
Bloom desc.
"Chromosome breakage syndrome- increased recombination events.
AJ founder mutation"
Telangiectatic skin rash following sun, small, learning disability, male infertility. Leukemia, lymphoma, Wilms tumor, oropharyngeal, GI, CRC, GU, breast, skin, and lung cancers
