Oncogenic mutations sites in relevant proto and oncogenes
Leerstof Oncology Ch7/14
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Vrije Universiteit Amsterdam (VU)
Biomedical Sciences
Oncology (AB_1184)
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Oncology Exam I
1
,Index
1 – Molecular Biology of Cancer ..................................................................................................................... 4
2 – The Cancer Genome: DNA, mutations, and carcinogenic agents ............................................................... 9
DNA aberrations ................................................................................................................................................ 9
(Ionizing) radiation ........................................................................................................................................... 11
(Non-ionizing) radiation ................................................................................................................................... 12
2 – The Cancer Genome: DNA repair and therapeutic strategies .................................................................. 13
DNA repair mechanisms ................................................................................................................................... 13
Radiotherapy of cancer .................................................................................................................................... 18
Chemotherapy of cancer .................................................................................................................................. 19
Hormone therapy of cancer ............................................................................................................................. 19
Drug and radiation resistance .......................................................................................................................... 19
Synthetic lethality ............................................................................................................................................ 20
Mutational signatures...................................................................................................................................... 20
3 – Regulation of Gene Expression ............................................................................................................... 21
Transcription factors (TF) ................................................................................................................................. 21
How to examine if a transcription factor has bound ................................................................................... 26
Chromatin structure and DNA packaging ........................................................................................................ 30
Micro RNA ........................................................................................................................................................ 34
Long noncoding RNAs ...................................................................................................................................... 35
Telomeres and telomerase ............................................................................................................................... 36
4 – Growth Factors and Oncogenes .............................................................................................................. 39
Protein modifications: protein phosphorylation .............................................................................................. 40
Protein modifications: interactions between proteins ..................................................................................... 41
Protein modifications: binding to small molecules .......................................................................................... 42
Signal transduction: relay system .................................................................................................................... 44
5 – The Cell Cycle (CC) .................................................................................................................................. 53
The basics ......................................................................................................................................................... 53
S-phase: DNA replication ................................................................................................................................. 55
M-phase: mitosis .............................................................................................................................................. 55
Control of transitions by cyclin-CDK complex ................................................................................................... 57
Control of transitions by checkpoints ............................................................................................................... 61
The cell cycle in cancer ..................................................................................................................................... 65
6 – Growth inhibition and tumor suppressor genes ...................................................................................... 68
2
,3
, 1 – Molecular Biology of Cancer
Incidence
Ø Absolute number of new cases in time frame
Ø About 124.000 new diagnoses were made in 2022
Ø Lower in low-income countries
o Diagnosis is not that well developed
o People die of other courses
o Lower change to develop cancer
o In Europe cancer is priority, in Africa it’s not
Prevalence
Ø Total number of people still alive and diagnosed with cancer in certain period
Ø 390.000 people in total were diagnosed with cancer in 2022
Mortality
Ø Number of patients who died as result of cancer within period
Ø Some cancers are low mortality (thyroid cancer)
Ø Some cancers are high mortality (lung cancer)
o Back in days, only men smoked, now also women
§ Women mortality increasing
§ Men mortality decreasing
Survival
Ø Percentage of patients still living at certain period after diagnosis
Ø After 20 years a small 20% of people diagnosed with cancer survived
Ø 5-year survival improved over 30% since 1980 due to better diagnosis and treatment
What is cancer?
Ø Group of diseases, over 100 cancer types
Ø Invasive, uncontrolled cell growth, angiogenesis and forming metastases
Ø Tumor is mass group of abnormal cells that form in the body, they can
o Not spread into, or invade, nearby tissues or other parts of the body (benign)
o Spread into, or invade, nearby tissues (malign and cancerous)
Ø Cancer is a malign tumor (invasive and spreading in other tissue)
Why is a malignant tumor life threatening?
Ø Disruption organ function due to invasion
Ø Cancer cells compete with normal cells for nutrients and oxygen
o Not only location of the tumor
o Whole body can be low energy
Ø Growing tumors can cause obstructions
4
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