Chapter 18: The genetics of Cancer

1. Chapter 18: The genetics of Cancer A presentation by Angelee, Skyler, and Jerri.

2. Introduction Cancer is genetic, but not usually inherited Characteristics of cancer cells Origins of Cancer Cells Genes associated with cancer A series of Genetic changes causes some cancers Environmental causes of cancer Human genome data tailor diagnosis and treatment

3. Did You Know? Introduction Cancerous tumors have been found on Egyptian mummies dating back to 3000 B.C. “This papyrus recounts the case of a ‘tumor against the god Xenus.’” (http://rex.nci.nih.gov/behindthenews/cioc/egyptians/egyptians.htm)

4. By 1600 B.C. Egyptians were trying to treat cancer. One remedy for uterine cancer was to put ground up dates and pigs brain into the vagina! Setmetnanch, anAncient Egyptianphysician is show to the right.

5. Hippocrates had named the disease “cancer” in 300 B.C. The tumor looked like a crab invading normal tissue. Cancer Tissue

6. We now know that cancer is a collection of diseases that are caused by mutations in somatic cells.

7. Cancer is genetic, but not usually inherited Tissue cells that do not follow mitosis grow into tumors Scientists can use dyes to find cancerous cells. Cancerous cells The different shades of color show how gene expression changes between normal and cancerous cells. MELANOMA CELLS

8. BENIGN OR It DOES NOT spread into other tissue. MALIGNANT ? It DOES spread into nearby tissue.

9. Metastasis

10. Cancer is genetic disease at the cellular level. Single gene disorders have faulty instructions in every cell. Cancer occurs in only a few somatic cells throughout a lifetime. Genes vary from families to families. Some are probably more prone to cancer than others. Only 10% of cases are inherited as single-gene disorders. So if you inherit a gene that is more prone to cancer, it will run in families. So, cancer is a somatic mutation in an affected person’s cell. It is not inherited! What does that mean? EXACTLY!

11. LOSS OF CELL CYCLE CONTROL LOSS OF CELL CYCLE CONTROL What causes cancer?

12. LOSS OF CELL CYCLE CONTROL If a checkpoint in the cell cycle control is not working properly, cancer will occur.

13. LOSS OF CELL CYCLE CONTROL • Cells divide more frequently than normal cells. Click here to see more What are some ways cells lose control?

14. LOSS OF CELL CYCLE CONTROL Loss of control over telomere length. Click here to see more What are some ways cells lose control?

15. CELL DIVISION CANCER CELLS LOSE SPECIALIZATIONS OR NEVER SPECIALIZE AND DIVIDE UNCEASINGLY. 50 or so “Hayflick limit for cultured cells” are ignored. Click here to go back

16. A. In normal, specialized cells telomerase is turned off and the cell division is stopped. B. In cancer cells telomerase is turned back on and cells continue to divide

17. Inherited vs. sporadic cancer What kind of cancer is inherited?

18. Inherited vs. sporadic cancer Sporadic cancer is in one single gene and is not passed down

19. Inherited vs. sporadic cancer Germline cancer is in every cell, including gametes.

20. Inherited vs. sporadic cancer But in Germline cancer the cancer is in every cell including gamates, so it is directly passed down. So, in sporadic cancer a gene mutates and a tumor is formed later in life.

21. Characteristics of cancer cells What are cancer cells like?

22. Characteristics of cancer cells Cancer cells divide more often or more times than the cells they came from. Then why does it take so long for cancer to grow?

23. Characteristics of cancer cells At first there are fewer cells so they divide more slowly. When the tumor gets bigger, the cells divide faster. So, that is why cancer spreads so quickly after it is diagnosed?

24. Characteristics of cancer cells Yes! Here, I will show you a picture! Yes!

25. Wow, it does change very slow. No wonder it is hard to detect for years.

26. Characteristics of cancer cells Anything else? Yes, I’ll show you a table.

28. CANCER TAKES YEARS TO SPREAD

29. ANGIOGENESIS Invasiveness allows cancer cells to squeeze into any space Tumor Cell secreted proteins NEARBY CAPILLARIES EXTEND BRANCHES

30. Origins of cancer cells There are many theories. Lets look at a few. Okay, but where does cancer start?

31. Origins of cancer cells • Cancer cells are more specialized than stem cells but less specialized than differentiated cells near them in a tissue. • Cancer has its own stem cells • Tissue level favours cells that can divide continually My friend Homer will tell us more.

32. Does cancer descend from a stem cell or arise from a specialized cell? A stem cells daughter becomes partially specialized, it is like putting your clothing on. Click homer to see more Click homer to see more Taking your clothing off is like a differentiated cell’s daughter shedding specializations Click below to move on. TISSUE BOTH CAUSE CANCER!

33. What about the tissue cells?

34. Click below to go on

35. Click below to go on

36. If the balance is shifted and more stem and progenitor cells are created, then the extra cells pile up and create tumors.

37. If an injury occurs and too many cells divide and try to repair the tissue, then an abnormal growth will appear!

38. Good job. You got it.

39. Now let’s go to Jerri for more information!

40. 18.4 Genes and their roles during carcinogenesis Oncogenes and proto-oncogenes Tumor suppressor genes DNA repair genes

41. Difference between oncogene and proto-oncogene Proto-oncogene is a normal version of gene, which controls cell division cycle. Oncogene is a mutated version of proto-oncogene, which triggers a cell division at wrong time & wrong place. Tumor suppressor gene mutation halts the normal suppression of cell division. DNA repair gene allows many mutations to accumulate.

42. A proto-oncogene can mutate into an oncogene when it is placed next to a gene that boots its expression (Kaposi sarcoma, T cell leukemia, Burkitt lymphoma and liver cancer caused by viruses), or it can be activated by active gene (a normal part of the genome) placed next to it (cancer of parathyroid gland.

44. Fusion protein causes Chronic myeloid leukemia

45. Gleevec Effective small molecules, which bind onto tyrosine kinase, stopping it from binding to ATP and setting off the cell division.

46. Tumor Suppressors Cause the cancers by deletion of a gene that halts the tumor formation. Retinoblastoma (rare childhood eye tumor) P53 (causes a variety of cancers) BRCA 1 & BRCA 2 (breast/ovarian cancer genes)

47. Retinoblastoma

49. Breast cancer Inherited or familial

50. BRCA 1 (Breast cancer predisposition gene 1) This mutation of a large protein residing in nucleus increases the risk of inherited ovarian and breast cancer. It is a mutation carried as an autosomal dominant trait with late onset. 80% chance of developing breast cancer 50% chance of developing ovarian cancer BRCA 2 (Breast cancer predisposition gene 2) The protein is even larger than BRCA 1 is most common among the Ashkenazim. 60-85% of developing breast cancer 10-20% of developing ovarian cancer but BRCA 2 increases the chances of colon, prostate, pancreas, gallbladder, skin & stomach cancers.