BB20023/BB20110 DNA & disease (cancer biology) Dr. Momna Hejmadi bssmvh@bath.ac.uk https://moodle.bath.ac.uk/moodle5/login/index.php How to access learning materials: Go to the URL above and click Yes to both security alert and display questions. LOGIN with your BUCS username & password. Click on the DNA and disease course listed to access all learning materials related to this unit. Any problems? Email me at bssmvh@bath.ac.uk (FIRST please ensure that you are registered to do the unit with Teresa Buckley bsstpb@bath.ac.uk)

How is this unit assessed? Multiple Choice Questions (20%) Nature of cancer, DNA replication, DNA damage and DNA repair Wed 31st OCT 11.15 - 12.05 3WN 2.1 (all except NS students) 8W 2.30 (Natural Sci students) EXAM essay (60%) Topics are Oncogenic viruses Apoptosis Oncogenes & Tumour suppressor genes Angiogenesis & metastasis Cancer therapy (4 lectures) Lab Report (20%) Peer assessed DNA repair practical

General Reading List The Biology of Cancer by Robert Weinberg (Garland Publishers ) Other useful books to consult Cancer Biology (2000; 2nd ed) by RJB King (Prentice Hall Publishers) DNA repair and mutagenesis (2002) by Friedberg EC, Walker g and Siede W Plus reviews / articles

All lectures & practicals by MVH

Cancers are clonal descendents of one cell Figure 18.18

Cancer arises by successive mutations in a clone of proliferating cells Figure 18.21

Cancer phenotype results from accumulation of mutations in the clonal progeny of cells Clone of cells overgrows due to accumulation of mutations controlling proliferation. Disseminates through bloodstream to other parts of body Forms tumor

Introduction: The 6 Superpowers

Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO STOP SLOW Most cells wait for a ‘Go signal before dividing. Cancer cells don’t bother waiting… they produce their own ‘Go’ chemical messages and continue dividing.

Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO 2 STOP SLOW Even if the neighbouring cells produce a ‘Stop’ signal, cancer cells override these signals and continue dividing.

Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO 3 Apoptosis 2 STOP SLOW Normal cells sometimes react to stress by triggering a ‘Self Destruct’ button and killing itself, but cancer cells sneak past these self destruct signals and continue to divide, thus accumulating more mutations.

Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO 2 STOP Apoptosis 3 SLOW 4 Food Supply Cancer cells make sure they can keep dividing by stimulating the growth of new blood vessels to keep their nutrient supply lines open.

Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO 2 STOP Apoptosis 3 SLOW 5 Immortality One of the key superpowers is immortality. Unlike normal cells which have a finite life span, cancer cells manipulate their own DNA (via repetitive DNA sequences called telomeres) to keep dividing for a lot longer. 4 Food Supply

Introduction: The 6 Superpowers Cancer Cell Normal Cell 1 GO 2 STOP Apoptosis 3 SLOW 6 Metastasis Most tumours that show these traits are trouble, but the lethal nature of cancer is due to its ability to spread to other location or metastasize. 90% of cancer deaths are due to metastasis. 4 Food Supply 5 Immortality

General cancer phenotype includes many types of cellular abnormalities

Changes that produce genomic and karyotypic instability Defects in DNA replication machinery – lost capability to reproduce genome faithfully Increase rate of chromosomal aberrations – fidelity of chromosome reproduction greatly diminished Feature Figure 18.16 b(1)

Changes produce genomic and karyotypic instability and often show gross rearrangements Normal cells Cancerous cells Feature Figure 18.16 b (2)

Changes that produce a potential for immortality Loss of limitations on the number of cell divisions Ability to grow in culture – normal cells do not grow well in culture Restoration of telomerase activity Feature Figure 18.16 c

Changes that enable tumor to disrupt local tissue and invade distant tissues Feature Figure 18.16 d Ability to metastasize Angiogenesis – secrete substances that cause blood vessels to grow toward tumor Evasion of immune surveillance

Some cancers run in families such as retinoblastoma Figure 18.20

Most cancers result from exposures to mutagens If one sibling or twin gets cancer, other usually does not Populations that migrate – profile of cancer becomes more like people indigenous to new location

Most cancers result from aging Figure 18.19

Tumours as complex tissues Figure 18.19

Reading – any one of … www.els.net