Oncologic disorders

Question 1

What is the overall contribution of BRCA1 and BRCA2 to overall breast cancer (%)

Answer 1

• 2%

Question 2

The BRCA2 protien is invloved in DNA repair and biallelic mutations in the BRCA2 cause ______ anaemia

Answer 2

Fanconi

Question 3

When should woman with BRCA1/2 mutations consider prophylactic salpingo-oophorectomy?

Answer 3

• once family planning is completed

Question 4

Prophylactic mastectomy has an efficacy of at least ___% in women classified as high risk on the basis of a family history of BRCA breast cancer

Answer 4

• 90%

Question 5

According to NCCN guidlines at what age should a woman with a BRCA mutation start to consider annual breast MRI with contrast and mammograms

Answer 5

• ages 30-75

Question 6

What are the NCCN guidlines concerning males with BRCA 1/2 mutations, breast cancer and prostate cancer

Answer 6

• Self and clinical breast exams starting at age 35
• Prostate cancer screening starting at 45 for BRCA2, can consider in BRCA1

Question 7

Autosomal dominant syndrome consisteing of characteristic GI harmatomas, mucocutaneous pigmentation (frekling of lips and perioral regions) and predisposition to GI and breast cancers

Answer 7

• Peutz-Jeghers syndrome (PJS)

Question 8

Autosomal dominant syndrome caused by the LKB1 (STK11) mutations: serine/threonin kinase on 19p13.3

Answer 8

• Peutz-Jeghers syndrome

Question 9

Women with Peutz-Jeghers syndrome and STK11 have a high risk for what female cancers

Answer 9

• Breast (32-54% risk)
• Endometrial (9%)
• Ovarian (21%)
• Cervical (10%)

** Colorectal cancer risk (39%)

Question 10

Examination to regonize feminizing features in males, as a sign of whattype of cancer in STK11 positive patients

Answer 10

• Testicular cancer

Question 11

These surveillance modalities are recommended by the age of 8 in STK11 positive PJS patients

Answer 11

• Small bowel CT,MRI or endoscopy
• Upper encoscropy

Question 12

• Autosomal dominant disorder
• Germline mutations in TP53, CHEK2

Answer 12

• Li-Fraumeni syndrome

Question 13

Protein product of CHEK2

Answer 13

Serine/threonine protien kinase

Question 14

Diagnostic criteria for Li-Fraumeni

Answer 14

• Proband with sarcoma <45
• 1st degree relative <45
• and 1st or 2nd degree relative <45

Question 15

Disease mechanism for Li-Fraumeni

Answer 15

• Abnormal DNA repair
• P53: determines whether cells undergo arrest for DNA repair or apoptosis
• CHEK2: checkpoint gene that is activated in response to DNA damage

Question 16

BRCA1 variant associated with 20-30% of Jewish women with early breast cancer

Answer 16

• 185delAG

Question 17

BRCA2 variant associated with 45-60% of Jewish women with ovarian cancer

Answer 17

• 6174delT

Question 18

Autosomal dominant familial cancer syndrome associated with APC gene.

Answer 18

• Familial Adenomatous Polyposis

Question 19

Which of these protiens associated with Lynch Syndrome (Hereditary nonpolyposis colon cancer) is NOT a DNA mismatch repair protein?

• MLH1
• MSH2
• MSH6
• PMS1

Answer 19

• PMS1
• protein homolog 2

Question 20

What is the 3,2,1 rule and what hereditary cancer syndrome is it used to predict?

Answer 20

• Identify individuals who are likely to be mutations carriers for Lynch syndrome
• Amsterdam II criteria
• 3 affected individuals (at least 1 st degree)
• 2 successuve generations
• 1 or more HNPCC related cancers <50yrs

Question 21

What is the most common extracolonic neoplasm associated with Lynch syndrome (HNPCC)

Answer 21

• Endometrial cancer

Question 22

Lynch syndrome tumours demonstarate microsatelite instability (MSI) secondary to defects in _____ genes

Answer 22

• Missmatch repair genes

Question 23

What percentage of markers must show expansion or contractionof repetative sequences in a tumour compared to normal, in order to be considered to have (high) microsattalite instability

Answer 23

• 30%

Question 24

Clinical diagnosis of MEN1?

Answer 24

• 2 or more MEN1 associated tumours or tumor in 1st degreee relative with MEN1
  
  • Parathyroid
  • Anterior pituitary
  • Enteropancreatic

Question 25

Responsible gene for MEN2?

Answer 25

* *RET*

Question 26

Clinical diagnosis of MEN2A?

Answer 26

* 2 or more * Medullary thyroid cancer * Primary hyperparathyroidism * Pheochromocytoma

Question 27

Clinical diagnosis of MEN2B

Answer 27

* Medullary thyroid carcinoma * Pheochromocytoma * Mucosal neuromas of lips and tounge * mylinated coneal fibres * Marfanoid habitus * Joint laxity * intestinal ganglioneuromas

Question 28

RET sequencing identifies the majority of variants in these exons?

Answer 28

* Exon 10 and 11 (95% MEN2A) * Exon 16 (95% MEN2B)

Question 29

Tumor syndrome associated with * Benign nerve tumors (bilateral aucoustic schwannoma) * miningiomas, ependymonas, astrocytomas) * Hearing loss, tinnitus, vertigo * Cataracts, mononeuropathy * Cafe au lait

Answer 29

* Neurofibromatosis Type II

Question 30

Major criteria of the syndrome shown in the pictures

Answer 30

* *PTEN* Harmatoma tumor syndrome * **_Cowden syndrome_** * Breast Cancer * Non-medullary thyroid * Macrocephaly * Endometrial carcinoma

Question 31

Spot diagnosis of syndrome shown in the picture

Answer 31

* *PTEN* harmatoma tumor syndrome * Bannayan-Riley-Ruvalcaba * Macrocephaly * harmatomous intestinal polyposis * lipomas * pigmented macules of the glans penis

Question 32

**_Plantar collagenoma_** is pathonomonic for what condition?

Answer 32

* PTEN Hamartoma tumor syndrome * Proteus syndrome * Rapidly progressive, asymmetric postnatal overgrowth of tissues, with hyperostoses, vascular malformations, dysregulation of fatty tissues (both atrophy and overgrowth), and skin manifestations such as verrucous epidermal nevi or cerebriform connective tissue nevi * risk of ovarian or parathyroid tumor in 2nd decade

Question 33

Spot diagnosis of condition shown in the pictures

Answer 33

* Tuberous Sclerosis: *TSC1* and *TSC2* * **Major features** Angiofibromas (≥3) or fibrous cephalic plaque Cardiac rhabdomyoma Cortical dysplasias, including tubers and cerebral white matter migration lines Hypomelanotic macules (3 to \>5 mm in diameter) Lymphangioleiomyomatosis (LAM) (see \*Note) Multiple retinal nodular hamartomas Renal angiomyolipoma (see \*Note) Shagreen patch Subependymal giant cell astrocytoma (SEGA) Subependymal nodules (SENs) Ungual fibromas (≥2) * **Minor features** "Confetti" skin lesions (numerous 1- to 3-mm hypopigmented macules scattered over regions of the body such as the arms and legs) Dental enamel pits (\>3) Intraoral fibromas (≥2) Multiple renal cysts Nonrenal hamartomas Retinal achromic patch

Question 34

Location of deletion syndrome associated with TSC2 and polycystic kidney disease?

Answer 34

* 16p13.3 * TSC2 lies immediately adjacent to PKD1 and large heterozygous deletions can result in the TSC2/PKD1 contiguous gene syndrome (PKDTS) * Individuals with the TSC2/PKD1 contiguous gene deletion syndrome are also at risk of developing the complications of ADPKD, which include cystic lesions in other organs (e.g., the liver) and Berry aneurysms.

Question 35

Clinical features of Von Hippel-Lindau syndrome

Answer 35

* Retinal angioma * Spinal or cerebellar hemangioblastoma * Adrenal or extra-adrenal pheochromocytoma (HTN) * Renal cell carcinoma * Multiple renal and pancreatic cysts

Question 36

The leading cause of mortality in von Hippel-Lindau syndrome

Answer 36

* Renal cell carcinoma

Question 37

Disease mechanism of Xeroderma Pigmentosum

Answer 37

* Impaired ability to sense, excise and repair UV-induced DNA damage

Question 38

Genes associated with Xeroderma Pigmentosum

Answer 38

* *XPA* * *XPC* * *ERCC2* * *POLH*

Question 39

What are the neurological complication of the shown condition

Answer 39

* Xeroderma Pigmentosum * acquired microcephaly * dec/absent DTR * progressive cognitive impairment * SNHL

Question 40

What are the ocular complication of the shown condition

Answer 40

* Xeroderma Pigmentosum * Photophobia * keratitis * atrophy of the eye lids * malignancy of the eye (melanoma, squamous cell and epithelioma)