Cancer Genetics Flashcards
What cancers are associated with VHL?
Hemangioblastomas (most common one associated with VHL!) These can present as retinal agiomas, cerebellar hemangioblastomas, and spinal hemangiomas.
Endolymphatic sac tumors
Epidydimal cysts
Pancreatic cysts and PNETs
Pheos (secrete only norepinephrine in VHL)
Clear cell renal cancer and renal cysts
Think Hippo with HERP (hemangio,endolymphatic,renal cell cancer,pheos)
What gene should you test for in any patient presenting with medullary thyroid cancer or C-cell hyperplasia?
RET (for MEN2)
What are the features associated with MEN2?
Medullary thyroid cancer (~100%)
Pheos (metanephrine predominant) (50%)
Hyperparathyroidism (10-20%)
What is the Carney Triad?
Gastric leiomyosarcoma
Pulmonary chondroma
Adrenal adenoma
What is the Carney Complex?
Skin pigmentation changes (nearly 100%)
Lentigines on lips, eyes, or genitalia, at least one blue nevus
Primary pigmented nodular adrenocortical disease
Pituitary adenomas
Cardiac myxomas
Breast adenomas
Thyroid nodules or cancer
Psammomatous melanotic schwannoma
Large cell calcifying Sertoli cell tumor (LCCST)
PRKAR1A gene
Birt Hogg Dube type of renal cell carcinoma
Chromophobe (most common), clear cell carcinomas, or mixed oncocytic
If you have multiple types of these skin findings it is pathoneumonic for Birt Hogg Dube
Fibrofolliculomas
HLRCC type of renal cell cancer
Papillary type II
If you see a child with hypopigmented macules and multiple kidney cysts, which contiguous gene deletion should you think of?
TSC2 and PKD1 (TSC and ADPKD)
What gene should you reflex to in a child with skin findings of NF1 but normal NF1 testing?
SPRED1
Major diagnostic criteria for Gorlin syndrome
Calcification of the falx (can see on skull Xray), jaw keratocyst (can see on Panorex), Palmar/plantar pits (can see best after soaking in water), multiple BCCs
Individuals receiving a clinical dx of NF2 must have what features
vestibular schwannomas AKA acoustic neuromas (typically bilateral, but can be unilateral)
Name some recessive/biallelic hereditary cancer syndromes
Ataxia telangiectasia Fanconi Anemia MYH-associated polyposis (MAP) Constitutional mismatch repair deficiency (CMMRD) Xeroderma Pigmentosum
Name some conditions you where you need to screen for Wilms tumor
Familial WT (FWT1 and FWT2 genes) Beckwith-Weidemann Isolated hemi-hypertrophy WAGR Denys Drash Li-Fraumeni Other overgrowth syndromes
What are some syndromes you can see non-medullary thyroid cancer in?
Carney complex 1
Cowden
FAP
Multinodular goiter
Epidermoid cysts are associated with which syndrome?
FAP
Angiofibromas are associated with which syndrome?
MEN1
Cutaneous leiomyomas are associated with which syndrome?
HLRCC
What is the purpose of the Bethesda criteria?
To identify a colorectal tumor that should be evaluated for MSI
If a breast lesion stains negative for e-cadherin, what type of breast lesion is it and which syndrome should you consider?
lobular lesion; HDGC
Attenutated FAP is associated with mutations in which parts of the FAP gene?
3’ and 5’ ends
Name some features you would expect to see in an MSI-H tumor
poorly differentiated, mucinous, signet ring cells, tumor infiltrating lymphocytes, medullary growth pattern, right-sided
You are seeing a woman in cancer clinic with a known familial mutation and her sister wants KFM testing. They mention Ashkenazi Jewish ancestry. What testing do you offer?
Multi-site 3 BRCA testing
Which two childhood tumors are most predictive of a TP53 mutation?
Adrenocortical carcinomas and choroid plexus tumors
Name 3 syndromes associated with hamartomatous polyps
Peutz-Jeghers
Cowden
Juvenile polyposis
Which MMR gene has a slightly higher risk for endometrial cancer than the rest?
MSH6
Which MMR gene is more common in Muir Torre syndrome? (Sebaceous adenomas)
MSH2
Which group of women does ovarian cancer screening have a high false positive rate in?
Premenopausal
What is the carrier rate of a BRCA1/2 mutation in Ashkenazi Jews?
1/40
Oral contraceptives are protective against which kinds of cancer?
Endometrial, ovarian
Which hereditary cancer syndrome does PARP inhibitors aid in treatment for?
HBOC; PARP inhibitors sensitizes tumor cells (especially those caused by BRCA1/2) to cytotoxic therapy and radiation therapy
What is the de novo rate in NF1?
50%
What is the de novo rate in NF2?
50%
At what age do children with NF1 have the majority of symptoms to meet clinical criteria?
8 years
What is the most prevalent feature in children with NF2?
Bilateral acoustic neuromas AKA bilateral vestibular schwannomas
What does renal involvement in patients with TSC consist of?
Kidney cysts, angiomyolipoma (most common, ~80%), clear cell carcinoma
Hereditary Papillary type I renal cell carcinoma is associated with which gene?
c-MET
What type of polyps are seen in Peutz-Jeghers syndrome and where are they most frequently located?
hamartomatous; small bowel (intussusception)
MEN1
Parathyroid, pituitary, pancreatic
Test calcium levels
Pituitary notes: prolactinoma, sexual dysfunction in males, amenorrhea in females
No surgery
MEN2A
RET gene
MTC, parathyroid, pheos
Remove thyroid by age 5 (check for pheos first)
MEN2B
RET gene
marfanoid habitus, MTC, pheos, mucosal neuromas
remove thyroid in infancy (check for pheos first)
