104
CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 11: O N C O G E N E S A N D C A N C E R
Summary:
A 32-year-old female with strong family history of breast, colon,
and ovarian cancer, who now presents with a fixed breast lesion that is biopsy-
proven carcinoma.
Most likely cancer gene: Breast cancer
(BRCA)
gene
Likely mechanism: Inhibition of tumor-suppressor gene
C L IN IC A L C O R R E L A T IO N
This young woman has developed breast cancer at age 32 years. Moreover, she
has two first-degree relatives with breast and/or ovarian cancer prior to
menopause. This makes
BRCA
gene mutation likely. The
BRCA1
gene resides
on chromosome 17. This gene encodes a protein which most likely is impor-
tant in deoxyribonucleic acid (DNA) repair. Thus, a mutation of the
BRCA
1
gene likely leads to abnormal cells propagating unchecked. A woman with a
BRCA1
mutation has a 70 percent lifetime risk of developing breast cancer,
and a 30 to 40 percent risk of ovarian cancer. The vast majority of breast can-
cer is not genetically based, but occurs sporadically. However, familial-based
breast cancers are most common because of
BRCA1
mutation.
BRCA2
is
another mutation that is more commonly associated with male breast cancer.
Other genetic mechanisms of cancer include oncogenes, which are abnormal
genes that cause cancer usually by mutations. Protooncogenes are normal
genes that are present in normal cells and involved in normal growth and
development, but if mutations occur, they may become oncogenes.
A PPR O A C H TO O N C O G E N E S
O bjectives
1.
Know the definitions of oncogenes and protooncogenes.
2.
Understand the role of promoter and repressor functions of DNA synthesis.
3.
Know the normal DNA replication.
4.
Be familiar with DNA mutations (point mutations, insertions, deletions).
5.
Know the process of DNA repair.
6.
Understand the recombination and transposition of genes.
D efinitions
Okazaki fragment: Short segments of DNA (approximately 1000 nucleotides
in prokaryotes, 100 to 200 nucleotides in eukaryotes) synthesized on the
lagging strand during DNA replication. As the replication fork opens,
the ribonucleic acid (RNA) polymerase primase synthesizes a short
RNA primer, which is extended by DNA polymerase until it reaches the
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