ONCOGENE AND TUMOR SUPRESSOR GENE

major functional classes cancer gene

1. oncogene

1. oncogene

• promote cell growth and differentiation

• gain of function mutation

• dominant gene : one mutated allele sufficient to cause oncogenic effect

mechanism ;

• translocation of oncogene next to actrively transcribed gene

• point mutation

• amplification by insertion of multiple copies of oncogene

• insertion of retrovirall promoter or enhances sequences

classification of oncogene based on the function of gene product

• growth factor = SIS coding for platelet derived growth factor

• receptors for growth factor = ERB-B coding for epidermal growth factor

• intracellular signalling mediators = RAS

• nuclear binding transcription factor = MYC

• cell cycle regulator = CCND1

• antiapoptotic regulators = BCL2

major functional classes cancer gene

2. tumor supressor gene

• prevent uncontrolled growth of cell

• loss of function mutation

• inheritance : recessive , both allele must be inactivated

• types of tumor suppressor gene

• caretaker = repair DNA damage , BRCA1 and BRCA2

• gatekeeper= induce apoptosis . RB1 and TP53

2 hit hypothesis

• both copies of tumor suppressor gene must be inactivated

• inherited cancer -1st hit: germline mutation—2nd hit: acquired mutation

• sporadic cancer - both hits: acquired mutation

LOS OF FUNCTIONAL TUMOR SUPRESSOR GENE AND INHERITED RETINOBLASTOMA SUSCEPTIBILTY

RB1 GENE (CHROMOSOME 13)

1. INHERITED RETINOBLASTOMA

• 1st germline mutation of one RB1 allele

• 2nd acquired mutation or loss of remaining RB1 allele in any retinal cell

• bilateral tumor

2. SPORADIC RETINOBLASTOMA

• acquired mutation in both RB1 allele in same cell

• unilateral tumors

Major functional classes cancer gene

1. oncogene

2. tumor suppressor gene

3. genes that regulate apoptosis

• overexpressed anti apoptotic gene (BCL2)

• underexpressed pro-apoptotic gene (BAX)

1. genes that regulate interaction between tumor cell and host cell

• enhance or inhibit recognition of tumor cell by immune system