WEEK 14 (Cancer) Flashcards
What is the difference between Carcinomas, Sarcomas and Hematopoietic & lymphoid malignant neoplasms?
Carcinomas = Cancer that forms in epithelial tissue
Sarcomas = Cancers that develop in the bones and soft tissues, including fat, muscles, blood vessels, nerves, deep skin tissues and fibrous tissues
Hematopoietic & lymphoid malignant neoplasms = Cancer of the blood or bone marrow
What is the difference between benign and malignant tumours?
BENIGN = grow only locally and cannot spread by invasion or metastasis
MALIGNANT = invade neighbouring tissues, enter blood vessels and metastasise to different sites
What factors contribute to genetic instability?
- Defects in DNA replication
- Defects in DNA repair
- Defects in cell-cycle checkpoint mechanisms
- Mistakes in mitosis
- Abnormal chromosome numbers
What are the causes of human cancer?
- Chemical exposure (tobacco smoke, diet)
- Radiation (UV, ionising)
- Infection (Hepatitis B, Helicobacter)
- Inherited familial cancer syndromes
How can Oncogenes and Tumour suppressor genes lead to cancer?
- ONCOGENES ACT IN A DOMINANT MANNER -> a gain-of-function mutation in a single copy of the proto-oncogene can drive a cell toward cancer
- LOSS-OF-FUNCTION MUTATIONS IN TUMOUR SUPPRESSOR GENES ACT IN A RECESSIVE MANNER -> function of both copies of the gene must be lost to drive a cell toward cancer
Which pathways are disturbed in human cancers?
- Alterations in cell proliferation
- Alterations in DNA damage response
- Alterations in cell growth
[these pathways regulate cell proliferation, cell growth and the cell’s response to DNA damage or stress]
What is the genetic basis of cancer?
- Proto-oncogene activation + loss of tumour-suppressor gene expression -> cancer
- Activation of antiapoptotic genes + loss of proapoptotic gene expression -> cancer
What is Multiple Endocrine Adenomatosis type 2 (MEN2)?
An autosomal dominant disorder where there is a mutation in the RET gene encoding a RECEPTOR TYROSINE KINASE
SYMPTOMS:
- Medullary carcinoma of the thyroid
What is Multiple Endocrine Neoplasia type 2B?
Same as MEN2A with additional symptoms:
- Thickening of nerves
- Development of benign neural tumours (NEUROMAS) on the mucosal surface of the mouth and lips
A proto-oncogene is activated by a chromosome mutation, usually through ___________________
translocation
What is Chronic Myelogenous Leukemia and what are the symptoms?
Chronic Myelogenous Leukemia is a disease in which the bone marrow makes too many white blood cells. It is caused by a translocation between chromosomes 9 and 22.
CAUSE:
Translocation moves the proto-oncogene ABL (a tyrosine kinase) from its normal position on chromosome 9q to the “BREAKPOINT CLUSTER REGION” gene (BCR) -> Enhanced TYROSINE KINASE activity of protein encoded by CHIMERIC GENE causes chronic leukaemia
SYMPTOMS:
- Feeling of fullness in the abdomen
- Fever
- Enlarged lymph nodes
- Night sweats
- Weight loss
- Loss of appetite
- Recurrent infections
What is Burkitt Lymphoma and what are the symptoms?
A B-cell tumour of the jaw that has an unusual geographical distribution
CAUSE:
MYC PROTO-ONCOGENE is translocated from its normal position at 8q to a position distal to the immunoglobulin heavy-chain locus at 14q -> Translocation brings enhancer/other transcriptional activating sequences near to the MYC gene
SYMPTOMS:
- Tumours of jaw/other facial bones
- If spread to CNS -> nerve damage, weakness and paralysis
- Loss of appetite
- Weight loss
- Fatigue
- Night sweats
- Unexplained fever
What is the importance of Telomerase as an Oncogene?
- Gene encoding telomerase is a REVERSE TRANSCRIPTASE that is required to synthesise the repeat “TTTAGG” as a component of telomeres at the ends of chromosomes
- As cells differentiate into somatic tissues, telomerase activity declines -> telomerase expression persists in tumor cells -> Inhibition of telomerase is used to treat cancer
What are two types of Tumour-suppressor genes?
- GATEKEEPERS = regulate cell growth directly
- CARETAKERS = involved in repairing DNA damage and maintaining genomic integrity
What is Retinoblastoma and what are the symptoms?
Retinoblastoma is a rare malignant tumour of the retina in infants. 40% is HERITABLE where the child inherits a mutant allele at the RETINOBLASTOMA LOCUS (RB1). 60% is SPORADIC where RB1 alleles in a single retinal cell have been inactivated independently (occurs in one eye only).
CAUSES:
A random mutation of RB locus in retinal cell completely removes inhibition of Rb protein -> affected cell grows into a tumour
SYMPTOMS:
- Vision problems
- Eye pain
- Redness of the white part of the eye
- A pupil that doesn’t get smaller when exposed to bright light
- Bleeding in the front part of the eye
- A different colour in each iris
SYMPTOMS THAT INDICATE NON-HEREDITARY RETINOBLASTOMA:
- One eye drifting towards centre
- Decreased vision
- Inflammation
- Glaucoma
- Pain in eye
- Redness in eye
