CTSN -

Oncogenes in Lung Cancer

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I. Classification
A. Dominant oncogenes

1. Alter one allele of a gene
2. Mutation results in overproduction of a protein or loss of regulatory function of protein production
3. Both result in uncontrolled cell growth and division

B. Tumor-supressor anti-oncogenes

1. Mutation on two alleles of a gene
2. Lose ability to control growth
3. Results in malignant transformation of the cell
4. Include inherited retinoblastoma

II. ras
A. Rat sarcoma
B. Expression frequently enhanced in pulmonary neoplasm (all histologic types, especially NSCLC)

III. myc
A. L-myc (homolog found in lung cancer), N-myc, c-myc, etc.
B. Expression is associated with uncontrolled proliferation
C. Cells express only one homolog at a time
D. SCLC - Three levels of expression:

1. Low
2. Medium - amplification from chromosomal duplication
3. High - gene amplification

E. Enhanced expression

1. Associated with treatment (chemo-tx), and with shortened survival
2. Probably a secondary event

IV.
A. Supressor gene
B. Found in many types of carcinoma
C. Mutations found frequently in lung cancer cell lines

V. HER -2/neu (c-erb-2)
A. Encodes for protein

1. Transmembrane protein related to tyrosine kinase activity
2. Significant homolgy with epidermal growth factor receptor

B. Expression in adenocarcinoma associated with ¯ survival
C. expressed more frequently in NSCLC
D. Radiolabeled monoclonal antibody may help image tumor

Gene	SCLC	NSCLC
Oncogene
myc	10%	rare
ras	rare	20%
Anti-oncogenes
gene not yet identified	100%	50-80%
rb gene	100%	15%
gene	100%	47%