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Genetic and Inheritance Patterns in Oncology and Hereditary Disorders
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Genetic and Inheritance Patterns in Oncology and Hereditary Disorders
Genetic and Inheritance Patterns in Oncology and Hereditary Disorders
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1
Question
What is the inheritance pattern of mutations causing Familial Adenomatous Polyposis (FAP)?
Answer
Autosomal dominant on chromosome 5
2
Question
Which syndrome includes FAP plus soft tissue or bone tumors?
Answer
Gardner syndrome
3
Question
Which syndrome includes FAP plus CNS tumors?
Answer
Turcot syndrome
4
Question
What translocation is overexpressed in follicular lymphoma?
Answer
t(14;18) translocation
5
Question
What does BCL-2 encode?
Answer
Anti-apoptotic molecule; promotes cell survival
6
Question
What is the genetic abnormality in chronic myelogenous leukemia (CML)?
Answer
t(9;22) translocation; Philadelphia chromosome; BCR-ABL fusion gene
7
Question
What is the mechanism of action of imatinib in CML?
Answer
Targets BCR-ABL tyrosine kinase
8
Question
Which proto-oncogene codes for serine-threonine kinase and is seen in some melanomas?
Answer
BRAF
9
Question
Which breast cancer tumor suppressor gene is associated with increased risk of breast and ovarian cancers?
Answer
BRCA1/2
10
Question
Which translocation overexpresses c-KIT in GISTs?
Answer
t(8;14) in Burkitt lymphoma; c-KIT codes for a transcription factor
11
Question
Which gene is mutated in Burkitt lymphoma, producing a starry sky histology?
Answer
c-MYC
12
Question
How does a 'motley mix' blood smear relate to leukemia?
Answer
Characteristic for CML with myeloid proliferation, low leukocyte ALP
13
Question
What is the target of erlotinib?
Answer
EGFR tyrosine kinase
14
Question
What does HER2/neu overexpression indicate in breast cancer?
Answer
Poor prognosis; targeted by trastuzumab (Herceptin)
15
Question
How does JAK2 mutation manifest in myeloproliferative disorders?
Answer
Increased proliferation of hematopoietic stem cells; seen in PV, essential thrombocytosis, myelofibrosis
16
Question
What mutation is commonly first in colorectal polyp progression?
Answer
KRAS mutation
17
Question
Which gene mutation is associated with familial multiple endocrine neoplasia type I?
Answer
MEN1; encodes hamartin and tuberin
18
Question
Which gene mutation causes hereditary non-polyposis colorectal cancer (HNPCC)?
Answer
MSH2/6 (mismatch repair genes)
19
Question
What developmental anomaly results from abnormal HOX gene expression, transforming vertebral identity?
Answer
Lumbar vertebrae develop as thoracic due to expression of cranial HOX genes at lumbar level
20
Question
What is the inheritance pattern of hereditary hemorrhagic telangiectasia (HHT)?
Answer
Autosomal dominant; no carrier state for AD disorders
21
Question
What mutation leads to retinoblastoma and why does the patient have preserved health?
Answer
Germline mosaicism; second hit in somatic cells causes tumors despite germline mutation being present
22
Question
What is the probability that two children will both carry the same diagnosis if the diagnosis is X-linked recessive G6PD deficiency?
Answer
1/16; each son has 1/2 chance of inheriting the mutation from carrier mother, so 1/4 for each child, squared for two children.
23
Question
What is the probability the patient and her husband will have a daughter who is a carrier for hereditary hemorrhagic telangiectasia?
Answer
Zero; no carrier state in autosomal dominant disorders.
24
Question
Why is there no carrier state in hereditary hemorrhagic telangiectasia?
Answer
Because it is an autosomal dominant disorder.
25
Question
In an autosomal dominant disorder, who can be a carrier?
Answer
No one; all are affected if mutated.
26
Question
How does incomplete penetrance affect individuals with a dominant mutation?
Answer
They may carry the mutation but not show the phenotype.
27
Question
What explains the patient’s unaffected health despite a family history of retinoblastoma and osteosarcoma?
Answer
Incomplete penetrance of the autosomal dominant retinoblastoma gene.
28
Question
What is the difference between incomplete penetrance and variable expressivity?
Answer
Incomplete penetrance: some with genotype do not phenotypically express; variable expressivity: varies in severity among those with the disease.
29
Question
Why is the patient's family showing these cancers likely to have incomplete penetrance?
Answer
Because not all with the mutation manifest the phenotype.
30
Question
What genetic mechanism explains why II-5 has a disease phenotype despite normal family history?
Answer
Incomplete penetrance of the autosomal dominant trait.