Human Genetics MT 3 pt 4

cancer potential

cell with accumulated DNA damage and mutations

what makes cancer cells different than normal cells?

• less specialized

• ignore signals telling cells to stop dividing

• influence normal cells, molecules and blood vessels that surround them (help feed tumor)

• evade immune system and influence it to help stay alive and grow

what are the 2 main properties of cancer cells?

• uncontrolled cel diviison

• ability of cells to spread to other sites in body (metastisize)

levels of cancer

• genome level

• cellular level

• whole-body level

genome level

• alterations

• point mutations

• copy number variants

• chromosome rearrangements

• aneuploidy

• changes in gene expression

cellular level

• disrupted pathways

• cell fate

• cell survival

• genome maintenance

whole-body level

• diagnosis

• symptoms

• tests

is cancer genetic?

yes

how is cancer genetic?

• some viruses carry genes that promote cancer

• specific chromosomal changes are found in certain cancers

what is the ultimate cause of cancer?

mutations

cell cycle checkpoints

• G 2/M

• M

• G1/S

G 2/M checkpoint

cell monitors completion of DNA synthesis and DNA damage

M checkpoint

cell monitors attachment of spindle fibers to chromosomes

G 1/S checkpoint

cell proceeds to S phase or enters inactive state

how does cancer begin?

• begins in single cell

• cell accumulates specific mutations over long period of time

• cells escape control of cell cycle and continue to divide and mutations continue to accumulate

is cancer the same in everyone?

no, each person’s cancer has unique combination of genetic changes

metastasis

• spread of cancer cells from original tumor to other parts of body

• form new tumors

• caused by cancer cells having reduced adhesiveness in membranes

tight junctions

water-tight seal between cells preventing leakage of substances

desmosomes

• attach cells together to prevent cells from stretching and tearing

• looser than tight junctions

gap junctions

connect cells while allowing materials to pass between cells

what leads to tumors?

unrestrained cell growth and division

telomerase

• specialized regions of chromosomes

• upregulated in cancer cells

types of cancers

• sporadic

• inherited

sporadic cancer

• majority of cases

• caused by gradual accumulation of mutations in somatic cells

inherited cancer

• minority of cases

• inherited mutant genes cause predisposition to cancer

• mutations carried in all cells in heterozygous state

• normal allele is lost

what cells are responsible for cancer?

• epithelial cells

• cause 80% of all cancers such as skin, lung, and breast cancer

• ex. epidermal stem cells responsible for everyday regeneration of different layers of epidermis

why do epithelial cells cause the most cancer?

because they are exposed to more environmental factors

3 main genes involved in cancer

• proto-oncogenes

• tumor suppressor genes

• DNA repair genes

tumor-suppression genes

• encode proteins that suppress cell division and regulate cell cycle

• both copies need to be mutated (recessive)

• act at control points in cell cycle

proto-oncogenes

• encode proteins that start, increase or maintain cell division

• only one copy is mutated (dominant)

• initiate or maintain cell division

retinoblastoma

• malignant tumor of eye arising in retinoblasts

• usually occurs in children

• loss of heterozygosity in tumor suppressor gene

oncogenes

• genes that induce or continue uncontrolled cell proliferation

• encode proteins that function as growth factors

ras proto-oncogene

mutation in ras proto-oncogene causes cell division to always be on