This document contains extensive notes of the lectures that belong to the first exam of oncology. Many pictures are included with an explanations and also things that were mentioned in the book but not during the lexctures are included. It is in it English because the exam will also be in English. ...
Oncogenic mutations sites in relevant proto and oncogenes
Leerstof Oncology Ch7/14
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Vrije Universiteit Amsterdam (VU)
Gezondheid En Leven
Oncology (AB_1184)
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Lectures Oncology Exam I
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Lecture 1 – Chapter 1 Introduction: the Nature of Cancer ..................................................................... 2
Lecture 2 – Chapter 2 DNA structure and stability: Mutations versus repair. ........................................ 9
Lecture 3 – Part of Chapter 2: Radiation and Chemical carcinogenesis................................................ 17
Lecture 4 – Chapter 3: Regulation of gene expression ......................................................................... 27
Lecture 5 – Chapter 4: Growth factor signaling and oncogenes ........................................................... 42
Lecture 6 - Chapter 5: The Cell Cycle ..................................................................................................... 55
Lecture 7 – Chapter 6: Growth inhibition and tumor suppressor genes .............................................. 64
Lecture 8 – Exam training ...................................................................................................................... 76
Lecture 9 – Molecular Diagnostics in Pathology ................................................................................... 80
Lecture 10 – Partical assignment: Introduction .................................................................................... 86
Practical assignment Molecular diagnostics quizzes ............................................................................. 89
1
,Lecture 1 – Chapter 1 Introduction: the Nature of Cancer
Molecular Biology of Cancer → Mechanisms, targets and therapeutics.
Incidence of cancer → The absolute number of new cases that is registered within a certain period
(mostly 1 year).
- To be able to follow the incidence in time, or to enable comparison between regions, the
incidence is mostly expressed as the number of new cases per 100.000 inhabitants/persons
each year → The crude incidence rate.
Prevalence of cancer → All persons who somewhere in time have been diagnosed with cancer and
are still living at a certain date.
- Hence, this is a diverse group, ranging from persons who have been cured from cancer in the
past to persons who just have been diagnosed with cancer.
- The period can be unlimited, but also defined.
- As an example → The 5-year prevalence on January 1st, 2010, comprises all still living people
who have been diagnosed with cancer during the previous 5 year.
Mortality of cancer → The number of patients who died as a results of cancer within a certain
period (mostly 1 year).
- The people who died in a certain year are not necessary the same people who were
diagnosed with cancer the same year.
Survival → The percentage of patients still living at a certain period after diagnosis.
- The presented survival is a relative survival that approaches the “cancer-specific survival”.
This means that the survival observed is corrected for the expected death within a
comparable population (with respect to country/region, gender, age and calendar year).
Cancer incidence
- How many new patients were diagnosed with
cancer in The Netherlands in 2021?
o 124.000 → 1 in every 137 people was
diagnosed with cancer last year.
- Over the years the incidence of cancer is
increasing except for 1 year (2020) because of
covid → Less people went to the doctor,
screening programs stopped.
- World wide data:
o In 2020 the incidence was almost 18
million and they expect the incidence
to rise to 27.5 million in 2040.
2
,Cancer prevalence and mortality in The Netherlands.
- 5 year cancer prevalence (2021) → 380.000.
- Mortality (2020) → 46.000.
o The last 4 years there is no increase in
mortality anymore.
Regional differences in cancer mortality.
- Picture shows how high cancers is ranked in
causes of death.
- Dark blue → First place in the raking.
- Top raking of cancer as leading cause of
premature death partly reflects marked declines
in mortality rates of stroke and coronary heart
disease in many countries.
Cancer mortality trends → 2010 versus 2000.
- Overall the relative mortality of cancer is decreased.
- But with lung cancer there is a change in mortality rate
for men and women → The mortality for men is
decreased and the mortality for women is increased.
o This is because there is an increase in women
smoking.
Survival time, as function of time after diagnosis.
- 5-year survival improved → 30% since 1980.
What is cancer?
- What is the clinical definition of cancer?
o Cancer is a group of diseases.
o More than 100 cancer types can be distinguished (or even every tumor is different?).
o Uncontrolled cell growth.
o Invasive and forming metastases.
▪ This has to occur otherwise it is no cancer.
3
, - Does a patient with a tumor always have cancer? → No.
o A tumor is a mass of cells.
o Not every tumor is invasive and metastasizing.
o Benign tumors are no cancer, only malignant tumors are cancer.
- Why is a malignant tumor life threatening?
o Invasion of organs disturbs organ function.
o Cancer cells compete with normal cells for nutrients and oxygen.
o Growing tumors can cause obstructions.
- What is the difference between carcinoma, adenocarcinoma, sarcoma and lymphoma?
o Carcinomas arise from epithelia (85% of all cancers).
o Adenocarcinomas arise from glandular tissues (e.g. breast).
o Sarcomas arise from mesodermal tissues (e.g. bone, muscle).
o Lymphomas arise from (progenitors of) white blood cells.
Why is the incidence of carcinomas much higher than of other cancers?
- Carcinomas are derived from epithelial cells.
- Epithelial cells align our body → Inside and outside.
- Epithelial cells are most exposed to carcinogens which lead to cancer formation.
Cancer is a disease of the genome.
- What is a carcinogen?
o A carcinogen is an agent causing cancer → Compound, radiation, etc.
o A carcinogen causes alterations in the DNA of a cell.
o Cancer cells contain many alterations in the DNA.
o The accumulation of mutations in the DNA of a cell causes stepwise development of
cancer (oncogenesis, carcinogenesis).
- Development of cancer → Oncogenesis.
o Oncogenesis → Birth of the cancer cell → From
normal cell to cancer cells.
o Normal epithelium → Hyperplasia → Dysplasia
→ Carcinoma in situ → Invasive carcinoma →
Lymph node and distant metastases.
o Cancer is clonal → All the cancer cells are
daughter cells from 1 cell where the cancer
started.
o Tumors are heterogeneous → During diving the
cells other mutations can occur leading to
different kind of daughter cells.
▪ So the tumor consist of many cells with
different genetic composition.
- Is cancer inheritable?
o No. Almost all of the mutations develop in somatic cells and will not be passed to
the next generation of offspring.
o However, some inherited germline mutations can increase the chance to develop
cancer and can be passed on to the next generation of offspring. These mutations
are rarely involved in causing cancer immediately.
4
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