2. pataloji 5-8 Flashcards
“What are the four major functional classes that cancer genes can be categorized into?”
Proto-oncogenes,
Tumor suppressor genes,
Genes that regulate apoptosis,
Genes that regulate interactions between tumor cells and host cells
What are the two groups of tumor suppressor genes?”
Governors” brakes on cellular proliferation.
E.g: (RB)
Guardians” responsible for sensing genomic
damage (P53)
Which gene is responsible for Retinoblastoma
RB
Which gene is responsible for Li-fraumeni syndrome
P53
Which gene is responsible for melanoma
CDKN2A
Which gene is responsible for Neurofibrobramatosis 1 and 2
NF1 and NF2
Which gene is responsible for FAP
APC
Which gene is responsible for Breast and ovarian tumors
BRCA1 BRCA2
Which gene is responsible for multibple endocrine neoplasia 1 and 2
MAN1 and RET
Which gene is responsible for for Bloom syndrom
blm
“How do driver mutations affect the development or progression of cancer?
alter the function of cancer genes
and thereby directly contribute to the development
or progression of a given cancer
“What is the typical example of point mutations in proto-oncogenes in terms of their function?”
A cardinal example is the RAS gene
“Which gene is most commonly affected by point mutations?”
TP53
What type of chromosomal translocation occurs in Burkitt lymphoma, and between which chromosomes does it occur?”
translocation, between chromosomes 8 and 14
Leads to overexpression of the MYC gene on chromosome 14
In follicular B cell lymphomas which Genes?
overexpression of the antiapoptotic gene
BCL2, on chromosome 18
Which chromosome is responsible for chronic myeloid leukemia (CML)
***Philadelphia (Ph)
translocation between chromosomes 9 and 22
BCR gene on chromosome 22 and the ABL gene on chromosome 9.
BCR-ABL fusion gene encodes?
tyrosine kinase with potent transforming activity
What genetic event is associated with retinoblastoma involving deletions at the 13q14 site, and which specific gene is affected by these deletions?”
RB Deletiation
What is the significance of the deletion of 17p in cancer genetics?
Deletion of 17p is associated with the loss of TP53, which is the most important tumor suppressor gene.
Which gene is clinically significant in neuroblastoma when amplified?
The NMYC gene is clinically significant in neuroblastoma when amplified.
Which gene is clinically significant in breast cancers when overexpressed/amplified?
HER2
What is the definition of aneuploidy in genetics?
fazla kromozom
.
.
What is CDKN2A, and what are its two encoded tumor suppressors?
p14/ARF colon and gastric cancers.
p16/INK4a is silenced in a wide variety of cancers.
Both p14/ARF and p16/INK4a affect the p53 and Rb pathways.
How can tumor suppressor genes be silenced?
Tumor suppressor genes can be silenced by hypermethylation of their promoter sequences.
What is the origin of malignant tumors?
Malignant tumors are monoclonal in origin.
Are tumor cells genetically homogeneous or heterogeneous?
Tumor cells are genetically heterogeneous.
ERB-B1 (EGF receptor): is overexpressed in ?
80% to 100%
squamous cell carcinomas of the lung
HER2/NEU (ERB-B2): is amplified in 25% to 30% of
breast cancers
HER2/NEU’ya karşı hangi ilaç kulanılır
TRASTUZUMABE.
Two important members in Downstream signal transducing proteins are?
RAS and ABL.
The RAS protein most commonly is activated by what klind of mutations
point mutations
How To inavcivate Ras protein
Ras protein is in activated when it is bound to an gdp
What is the effect of GTPase-activating proteins (GAPs) on RAS Protein
Gap Hydrolase Gtp to Gdp and ras binds to gdp
What does activation of RAS situmulalate
proliferation.
What is ABL Protein
ABL is
non–receptor-associated protein
has a tyrosine kinases activity
act as a signal transduction molecule.
Where van BCR-ABL kinase inhibitors can be used
myelogenous leukemia
BCR-ABL kinase inhibitors. are kind of ….. thearapy
targeted therapy
Nuclear transcription factors ARE?
**
MYC
MYB
JUN
FOS,
REL oncogenes
NTFs regulate the expression of growth-promoting genes,
such as ……
cyclins and CDKs
MYC genes generaly involved with?
human tumors
MYC can activate some gf including?
cyclin dependent kinases) CDKs,
What does (cyclin dependent kinases) CDKs, DO?
drive cells into the cell cycle
Genes repressed by MYC include the
CYD inhibitors:
(CDKIs).
What cause Burkitt lymphoma,
Dysregulation of the MYC gene resulting from a t(8;14)
translocation
What is the two main cheackpoint of cell cycle
G1/S transition
G2/M transition
G1-S transition, is regulated by proteins called?
CYCLINS
CDKs acquire catalytic activity by binding to and
forming complexes with the?
cyclins
What does CDK–cyclin kompleks
phosphorylate crucial target proteins that drive the cell through the cell cycle.
The activity of CDK–cyclin complexes is regulated by CDKIs, which enforce cell cycle checkpoints.
What are the İmp. examples of this proteins
retinoblastoma protein (Rb)
Or enter a nonreplicative state called senescence, primarily via?
p53-dependent mechanisms
Which CDKIs proteins inhibits CDKs Broadly
p21 (CDKN1A), p27 (CDKN1B), and p57 (CDKN1C)
cyclin CDK4 VE cyclin CDK6’yı inhibe eden proteinler hangileridir
p15 (CDKN2B), p16 (CDKN2A), p18 (CDKN2C), and p19 (CDKN2D)
Bunlar INK4 proteinleri olarak da anılır
INK4 proteinleri nelerdir
p15 (CDKN2B), p16 (CDKN2A), p18 (CDKN2C), and p19 (CDKN2D)
The cyclin D genes are over expressed in which cancers
breast,
esophagus,
liver,
lymphomas
plasma cell tumors.
Amplification of the CDK4 gene occurs in ?
melanomas, sarcomas, and glioblastomas.
deletion or inactivation of p16-CDKN2A is seened in?
pancreatic carcinomas
glioblastomas,
esophageal cancers,
non–small cell lung carcinomas
soft tissue sarcomas
bladder cancers.
Patients with familial retinoblastoma also are at greatly increased risk for development of ………..
osteosarcomas
hypophosphorylated Rb inhibits?
inhibits the E2F family of transcription factors, preventing transcription of cyclin E.
Growth factor signaling leads to cyclin D expression and activation of ………..
cyclin D–CDK4/6 complexes
cyclin E stimulates ……
DNA replication and progression
At least one of the four key regulators of the cell cycle
(…….., ……. , …….. , ……. ) is mutated in most human cancers
CDKN2A
cyclin D
CDK4
Rb
………… is a protein that targets p53 for destruction
MDM2
CDKN1A (p21)’in oluşması için hangi protein gerekli
P53
What p21 protein does
The p21 protein, inhibits cyclin–CDK complexes and prevents phosphorylation of Rb, thereby arresting cells in the G1 phase.
Gadd45 proteini ne uyarır
P53
Gadd45 proteinin ne yapar
Dna Repair
How Doeas P53 mediated?
by several pro-apoptotic genes such as
PAX BUMA
**
inherit a mutant TP53 allele causes?
LI FRAUMENI SYNDROME
……….. and ….. and ….. can bind
to normal p53 and nullify its protective function.
HPVs, HBV, and EBV
TGF-β is a ?
inhibitor of proliferation
In 100% of pancreatic cancers and 83% of colon cancers, at least one
component of the
TGF-β pathway is mutated
TGF-β pathway is mutated in?
In 100% of pancreatic cancers and 83% of colon cancers
………….. mediates cell–cell contact in epithelial layers
E-cadherin
NF2 nedir?
Bu gen, hücre büyümesini düzenlemeye yardımcı olan nörofibromin adı verilen bir protein üretir. Mutasyona uğramış gen, hücrelerin kontrolsüz büyümesine izin veren nörofibromin kaybına neden olur. NF2 geni, 22. kromozom üzerinde bulunur ve tümörleri bir protein üretir.
HOW adenomatous polyposis coli (APC) acts
behaves as a typical tumor suppressor gene
Warburg effect nedir?
Onkolojide, Warburg etkisi, çoğu kanser hücresinin enerjiyi ağırlıklı olarak normal hücrelerde gözlendiği gibi mitokondride ‘olağan’ sitrik asit döngüsü ve oksidatif fosforilasyon yoluyla değil, daha az verimli bir ‘aerobik glikoliz’ işlemi yoluyla ürettiği gözlemidir
“glucose hunger seened with ….. via injecting ……..
PET
18F-fluorodeoxyglucose
Short telomeres is recognized by the DNA repair
machinery, leading to cell cycle arrest and senescence,
mediated by ………………….. and …………
TP53 and RB.
The prototypical angiogenesis inducer is?
VEGF
The prototypical angiogenesis inhibitor is?
Damarlarda kan pıhtısı oluşumu.
thrombospondin-1. THbs1
hypoxia-inducible factor-1α (HIF-1α) is an
oxygen-sensitive transcription factor.
in normal circumtances ……… … protein destroys HIF-1α
von Hippel–Lindau protein (VHL)
lack of oxygen prevents ……… recognition by VHL, and it is not destroyed.
HIF-1α
VHL mutations cause
VHL SYNDROME
hereditary renal cell cancers,
pheochromocytomas,
hemangiomas of the central nervous system,
retinal angiomas,
renal cysts
………. molecules keep the cells together.
E-cadherin
.
.
………..is the final step of invasion, pushing tumor cells
through the degraded basement membranes and zones of matrix
proteolysis
Locomotion
The second step in invasion is
local degradation of the basement membrane and interstitial connective tissue
The third step in invasion
involves changes in attachment of tumor cells to ECM proteins
Human breast cancer cells chemokine receptors are?
CXCR4 and CCR7.
The ligands for these receptors (chemokines CXCL12 and CCL21
………….., an enzyme involved in melanin biosynthesis that is
expressed only in normal melanocytes and melanomas.
tyrosinase
tyrosinase, an enzyme involved in ………biosynthesis that is
expressed only in normal melanocytes and melanomas.
melanin
Tyrosinase, an enzyme involved in ………biosynthesis that is
expressed only in normal ……… and ……….
melanocytes and melanomas.
Hereditary nonpolyposis colon carcinoma
(HNPCC) syndrome
Neden önemli
The role of DNA repair genes in predisposition to cancer is
illustrated dramatically by HNPCC.
cecum and proximal colon’u etkiler
Xeroderma pigmentosum nedir?
defective DNA repair sonucu oluşur
sun-exposed skin kansere sebep olabilir
nucleotide excision repair system düzgün çalışmaz
The gene mutated in ataxia-telangiectasia is
ATM,
,
hereditary breast cancer caused by …………..
Mutations in two genes
BRCA1 and BRCA2
…………., that carry out V(D)J segment recombination
RAG1 and RAG2
RAG1 and RAG2, that carry out …………………………….
V(D)J segment recombination
Tumor-Promoting Inflammation as Enabler of Malignancy?
Barrett esophagus,
ulcerative colitis,
H. pylori gastritis,
hepatitis B and C,
chronic pancreatitis
In addition, neutrophils; reactive oxygen species
……………..is a naturally occurring agent produced by some
strains of Aspergillus, a mold that grows on improperly stored
grains and nuts
Aflatoxin B1
Aflatoxin B1, produce characteristic mutations in the ……… gene
TP53
ionizing radiation causes to?
A) Chromosome breakage,
B) Translocations,
C) Less frequently, point mutations
Natural UV radiation derived from the sun can cause skin cancers
melanomas, squamous cell carcinomas, and basal cell carcinomas
UV damage DNA by forming ………….
pyrimidine dimers
Patients with the inherited disease xeroderma pigmentosum have a defect in the ……………….. pathweay
nucleotide excision repair pathway
caues skin cancers
……………………………………..Can code TAX protein which prolipherates T cells that cause T cell leukemia/lymphoma
human T cell lymphotropic virus-1 (HTLV-1)
human T cell lymphotropic virus-1 (HTLV-1) Can code …………. which prolipherates T cells that cause T cell leukemia/lymphoma
TAX protein
human T cell lymphotropic virus-1 (HTLV-1) Can code TAX protein which prolipherates ………… that cause T cell leukemia/lymphoma
T cells
human T cell lymphotropic virus-1 (HTLV-1) Can code TAX protein which prolipherates T cells that cause …………..
T cell leukemia/lymphoma
***Four DNA viruses:
HPV,
Epstein-Barr virus (EBV
Kaposi sarcoma herpesvirus (KSHV,) [HHV-8]),
Hepatitis B virus (HBV)
high-risk HPVs (**types ………) cause several cancers, particularly squamous cell carcinoma of the cervix
16 and 18
high-risk HPVs (**types 16 and 18) cause several cancers, particularly …………
squamous cell carcinoma of the cervix
HPV can be related to products of two early viral genes, ……….
E6 and E7.
E7 inactivates the………. and ……….
CDKIs CDKN1A/p21 and CDNK1B/p27
The E6 protein binds to and mediates the degradation of …..
p53
Epstein-Barr Virus linked with …. diseases
Burkitt lymphoma
B cell lymphomas
Hodgkin lymphoma
nasopharyngeal carcinoma
gastric carcinomas
NK cell lymphomas
Burkitt lymphoma is endemic in certain parts of ……and is sporadic elsewhere.
Africa
EBV uses the complement receptor ……. to attach to and
infect B cells.
CD21
Relationship between Chronic HBV /hepatitis C virus (HCV) can cause?
hepatocellular carcinoma
H. pylori infection is genesis of both ……… and…..
gastric adenocarcinomas and gastric lymphomas
gastric lymphomas reffered as
MALT lymphomas.
