molecular basis of cancer

CANCER PATHOGENESISFacilitator: Bethy S. Hernowo,

dr., SpPA (K), PhD. Akhmad Mustafa, dr. (Urology)

Dedi Farokka, dr. (General Surgery)Farry, dr. (Orthopaedic and

Traumatology)Erwin Wijatmiko, dr. (Neurosurgery)

• Neoplasia: New growth• Neoplasma: abnormal mass of tissue the

growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after the cessation of the stimuli which evoked the change.

• Neoplasm BenignMalignant

Benign microscopic and gross characteristics are considered to be relatively innocent, implying that it will remain localized, it cannot spread to other sites, and is amenable to local surgical removal

GENE DEFECTS IN TUMOR DEVELOPMENT

• Balanced translocations• Deletions• Amplifications• Lost/Gain a whole chromosome

Translocations

Deletions

• Deletions: loss of parts of a chromosome• Can results in inactivation of tumor supressor

gene• Most common seen in nonhematopoietic solid

tumors

Gene Amplification

NONLETHAL GENETIC DAMAGE

Four classes of normal regulatory genes:• growth-promoting proto-oncogenes• growth-inhibiting tumor suppressor genes• genes that regulate programmed cell death

(i.e., apoptosis)• genes involved in DNA repair

Proto-Oncogenes

• Proto-oncogenes: normal cellular genes whose products promote cell proliferation

• Oncogenes: mutant versions of proto-oncogenes that function autonomously without a requirement for normal growth-promoting signals

Tumor Supressor Gene

• Tumor suppressor genes encode proteins that inhibit cellular proliferation by regulating the cell cycle

• Both copies of the gene must be lost for tumor development, leading to loss of heterozygosity at the gene locus

Genes that Regulate Programmed Cell Death

Genes Involved in DNA Repair