11353021
Description
Flashcards by Anna Hogarth, updated more than 1 year ago
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Created by Anna Hogarth
over 6 years ago
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| Question | Answer |
| How many people die from cancer in the UK every year? What portion of total deaths in the UK per year is this? Which cancers make up half of the total cancer deaths? (4) | 1) 160,000 2) 1/3 3) Lung, bowel, breast, and prostate cancer |
| What % of cancers occur in children (0-14)? | < 1% |
| Of total cancer diagnoses, how many occur in people aged over 65? | 3/5 |
| Which is the most common cancer in the UK? | Breast cancer - 15% of cancer cases (although it is rare in men) |
| What is the most commonly diagnosed cancer in the 0-14 female group? 25-49 female group? | 1) Leukaemia 2) Breast |
| In which age group is lung cancer most commonly diagnosed in males? In what age group are germ cell tumours most commonly found in males? | 1) 75+ (prostate cancer is the most common in males over 50) 2) 15-24 |
| How many different types of cancer are there? What are they characterised by? | 1) More than 200 2) Unregulated growth of malignant tumours |
| How far can localised cancers spread? | Can invade surrounding tumours and metastasise to other sites |
| What are solid cancer or haematological malignancies derived from? | Hematopoietic and lymphoid tissues |
| How do cancer cells differ to normal cells? | They don't need signals to survive |
| Give 7 characteristics of the physiology of cancer cells | 1) Growth signals are not required for cell survival, growth and differentiation 2) Unresponsiveness to growth-inhibitory signals 3) Evasion of apoptosis 4) Defects in DNA repair 5) Cells becomes immortal 6) Ability to invade and metastasise 7) Angiogenesis is sustained and increased |
| What is carcinogenesis? | A multi-step process that usually requires several mutations to initiate cancer |
| What are the steps in carcinogenesis (particularly colon cancer) and the mutations which could occur at each stage? | 1) Normal epithelium - mutation in adenomatous polyposis coli 2) Hyperplasia - mutation in K-ras 3) Adenoma (polyps) - deletion of p53 4) Adenocarcinoma (colon cancer) - further mutations 5) Metastatic cancer |
| Define carcinogenesis | A multistep process of transformation of a normal cell to a cancer cell |
| Define transformation | The conversion of one cell phenotype to another |
| Define carcinogen | An agent (chemical, radiation or microbial) that induces changes to a cell population that can cause cancer |
| Give two examples of a microbial which can cause cancer (and name the cancer) | 1) Epstein Barr virus - gastric carcinoma (9%) 2) Human herpesvirus 8 (HHV8) - Kaposi's sarcoma (skin and mouth) |
| Define differentiation | The process by which a cell develops or matures which allows it to perform a specific function |
| What do most cancer arise from? | Sporadic mutations |
| What are the three main groups of genes involved in cancer? | 1) Oncogenes 2) Tumour suppressor genes 3) DNA repair genes |
| What is the imbalance in cancer? | Proliferation and cell survival vs cell cycle arrest and apoptosis |
| What is an oncogene? | Gene that encodes protein capable of inducing cancer |
| What is the normal gene from which an oncogene derives? | A proto-oncogene |
| What do proto-oncogenes regulate? (2) | 1) Cell proliferation 2) Differentiation |
| What do many proto-oncogenes encode? What activates them? | 1) Growth factors, growth factor receptors or signaling molecules. 2) Mutations |
| What happens when a proto-oncogene is mutated into an oncogene? | Enhance signalling pathways in an uncontrolled way - leads to uncontrolled growth and/or cell division and reduced differentiation |
| What are the five categories of proto-oncogenes? | 1) Growth factors 2) Growth factor receptors 3) Signal-transduction proteins 4) Transcription factors 5) Pro or anti-apoptotic proteins |
| What do the mutations in the proteins in the previous card give rise to> | Dominantly active oncogenes - gain of function or increased expression |
| What underlies hyperplasia? What is it not? | 1) Autocrine loops 2) Genes are not mutated - not cancer |
| What underlies benign prostatic hyperplasia? | Increased VEGF |
| What underlies glioblastomas? | Increased PDGF |
| What has been found to be elevated in esophageal cancer? | TGFa |
| What does overexpression of growth factors of growth factor receptors lead to? | Uncontrolled activation of signalling pathways: 1) Uncontrolled growth 2) Survival of cells containing mutations 3) Invasion of tumour cells 4) Migration of tumour cells |
| What are two classes of receptors which are commonly overexpressed in cancer? What does this cause? | 1) HER2 and ErB2 2) Unregulated dimerisation and therefore activation of the receptor - this leads to activation of the receptor in the absence of growth factor |
| Where is the Her2 gene located? | Chromosome 17 |
| What is K-ras? | An oncogene - mutation in ras (signal transduction protein) results in k-ras. |
| How does k-ras result in cancer? | Hydrolysis of bound GTP occurs very slowly on this mutated version of Ras. Effectives this means that Ras is always in the Ras-GTP state, and is continually active. The accumulation of the active state Ras leads to constant activation of the ERK/MAPK pathway and continuous proliferation. |
| What % of patients with lung adenocarcinomas (NSCLC) have tumours associated with KRAS mutations? | 15-25% |
| What % of patients with colorectal have tumours associated with KRAS mutations? In relapsed patients? | 1) 30%-50% 2) 80% |
| What % of patients with pancreatic ductal adenocarcinomas have tumours associated with KRAS mutations? | More than 95% - has a very poor prognosis |
| What does KRAS stand for | Kirsten rat sarcoma viral oncogene homolog |
| What % of NSCLC cases are associated with a EGFR mutation? Glioblastomas? | 1) 10% 2) 20% |
| What % of colorectal cancers are associated with a EGFR overexpression? Pancreatic cancer? Lung cancer? Non-small cell lung cancer? | 1) 27-77% 2) 30-50% 3) 40-80% 4) 14-91% |
| What % of pancreatic cancers are associated with a RAS mutations? Papillary thyroid cancer? Colon cancer? Non-small cell lung cancer? | 1) 90% 2) 60% 3) 50% 4) 30% |
| What % of melanomas are associated with a B-Raf mutation? Papillary thyroid cancer? Colon cancer? | 1) 70% 2) 50% 3) 10% |
| What is one of the most frequently mutated transcription factors in cancer? | c-MYC proto-oncogene - 50% of cancers |
| Other than mutation in c-MYC, how else can c-MYC lead to cancer? What does c-MYC promote? | 1) Translocation 2) Transcription of cyclin genes, which promote cell cycle progression |
| What does elevation of the gene product of c-MYC correspond with? | 1) Tumour aggression and poor clinical outcome |
| What is Burkitt lymphoma caused by? How does C-myc relate to breast, colon and lung cancer? | 1) Translocation of c-MYC 2) Overexpression |
| How doe MYC overexpression induce tumorigenesis? | Causes the evasion of multiple tumour-suppressing checkpoint mechanisms including: 1) Proliferative arrest 2) Apoptosis 3) Senescence Important to note that MYC overexpression of MYC alone cannot induce tumorigenesis |
| How do cancers develop the ability to evade apoptosis? (2) WHat does this result in? | 1) Up-regulation of anti-apoptotic proteins 2) And/or downregulation of pro-apoptotic signaling pathways This allows cancer cells to survive even when challenged with chemotherapeutic or DNA-damaging compounds that would normally trigger cytotoxic responses |
| What do BAX and Bcl2 regulate? What doe they each promote? | 1) Apoptosis 2) Excess BAX causes apoptosis through Bax-bax homodimer (otherwise in heterodimer with Bcl2) 3) Excess BCL-2 blocks apoptosis (bcl-2 homodimer forms), promoting immortality of the cell |
| How do some B-cell lymphomas evade apoptosis? | Bcl-2 gene on chromosome 18 translocates to chromosome 14 and is put under control of the IgH (immunoglobulin gene) promoter. |
| What happens to tumour suppressor genes in cancer? | Many cancer cells harbour a loss of function of tumour suppressor mutations - less cell growth restriction is advantageous to tumour survival |
| How do tumour suppressor gene usually restrict cell proliferation? | 1) Control cell cycle and division 2) Induce apoptosis when other mechanisms have found |
| Describe the effects of mutations in tumour suppressor genes (3) | 1) Act recessively to release cells from growth control, increasingly the probability that the mutant cells will become tumour cells 2) Greatly increase the probability of mutations in the other protein clases 3) May prevent apoptosis or allows cell division of cells which contain mutations |
| What are gatekeeper genes? What is their function? Give two examples. | 1) Tumour suppressor genes 2) Stop cell cycle progression when DNA damage is detected 3) p53 - transcription factor; pRB - transcription factor |
| What is the most common genetic alteration in human cancers? | Mutations in p53 gene |
| What activates p53? | DNA damage, hypoxia or cell injury |
| What does p53 usually do? | Activates p21 - inhibits cyclin complexes and so prevents cell leaving G1 and entering S1. Cell cycle arrest allows DNA repair or entry to apoptotic pathway |
| What do mutations in p53 cause? | Allows cells to progress through cell cycle with DNA damage. Cells accumulate mutations which become cancerous through cycles of DNA damage and cell proliferation |
| What does pRB do? | Prevents cell cycle progression past G1 phase by inhibiting expression of S-phase genes. |
| What do mutations in pRB cause? What is the incidence of this? | 1) Retinoblastoma 2) 1: 20,000 (birth to 8 years) |
| What are the caretaker genes? What are their functions? (2) Give two examples. | 1) DNA repair genes 2) Maintain genomic stability and repair DNA damage during cell cycle arrest 3) BRCA (DNA repair proteins), MMR (mismatch repair genes) |
| What are the most commonly mutated genes in familial breast cancer and ovarian cancer? | BRCA1 and BRCA2 |
| What risk do carriers of mutant BRCA1 and BRCA2 have? | 50-70% risk of developing breast cancer before the age of 70 |
| What % of familial breast cancer do BRCA1/2 germline mutated alleles cause? Ovarian cancers? | 1) 50% 2) 70-80% |
| What are the normal functions of the BRCA1/2 proteins? | Directly involved in repairing damaged dsDNA crosslinks at the G2/M checkpoint |
| What does loss of the BRCA1/2 function result in? | Strand breaks and aneuploidy after division |
| What does BRCA1 do/interact with? (4) | 1) Interacts with several cyclins and CDKs 2) Triggers activation of CDK inhibitor - p21WAF-1 3) Activates P53 Therefore controls cell cycle 4) DNA repair processes |
| What happens in BRCA1 deficient cells? | Genomic instability |
| What is the primary function of BRCA2? | Facilitate homologous recombinarion |
| What happens in BRCA2 deficient cells? | Defective in recruiting RAD51 (ssDNA binding protein) to sites of DSBs and in repairing DSBs by homologous recombination |
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