Tumor arising from all 3 germ cell layers

Found in ovary and testes

a mass of disorganized by mature, specialized tissue/cells that are indigent to that site

i.e. lung mass with cartilage, vessels, and bronchial epithelium

Ectopic placement of normal tissue

e.g. pancreatic tissue in wall of duodenum

Paraneoplastic syndrome and associated cancers

- hypercalcemia or Cushing's syndrome

- Acanthosis nigricans

- hypertrophic osteoarthropathy

- migratory thrombophlebitis (Trousseau syndrome)

Hypercalcemia or Cushing's syndrome:

- lung cancer

Acanthosis nigrans:

- gastric and lung cancers

Hypertrophic osteoarthropathy:

- bronchogenic carcinoma

Migratory thrombophlebitis (Trousseau):

- pancreatic and lung cancer

Proto-oncogenes

- name them

RAS

MYC

ABL

Translocated from chromosome 8→14

Disease = Burkitt's lymphoma {t(8;14)}

MYC is a transcription factor that gets translocated into an active gene; sustained levels cause continued proliferation

Translocation from chromosome 9→22

Disease = chronic myelogenous leukemia

ABL/BCR fusion protein has potent unregulated TKase activity, activating JAK/STAT and MAP pathways → proliferation

Tumor suppressor genes

- name them

Retinoblastoma (Rb)

p53

INK4a/ARF locus

APC/ β-catenin

NF-1 gene

PTEN

Binds E2F preventing entry to S-phase

cyclin D/CDK4 or cyclin D/CDK6 phosphorylate Rb causing it to be degraded and allows E2F to enter nucleus and activate genes for proliferation

Arrests cell cycle in presence of stressors such as hypoxia or DNA damage

Promotes DNA repair via p21 and apoptosis via BAX

Promotes synthesis of thrombospondin-1, an anti-angiogenesis factor

P16INK4a blocks cyclin D/CDK4 from phosphorylating Rb thus preventing cell proliferation

LOF mutation seen in cervical cancer

APC regulates β-catenin levels via degradation

β-catenin can translocate to nucleus and stimulate proliferative genes

Homozygous mutations of APC → uncontrolled cellular proliferatoin

Familial adenomatous polyposis from loss of both APC genes

Neurofibromin inactivates RAS

Neurofibromin mutation allows uncontrolled RAS activity and thus hyperproliferation

Disease is neurofibromatosis

PTEN increase the transcription of p27, a CDK inhibitor

Loss of PTEN = uncontrolled proliferation

Endometrial carcinomas and glioblastomas

Overexpression of BCL-2 (antiapoptosis)

Loss of p53 → ↓BAX → ↑BCL-2:BAX → ↓ apoptosis