14 - Cytogenomics of Cancer Flashcards
Mosaicism
Presence of two or more cell populations each with its ‘personal’ genome, in an individual developed from a single fertilised egg
Chimera
Two or more cell populations derived from distinct fertilised eggs
Examples of chimera
- Fusion of DZ twins
- Transplantation
Where does mosaicism occur
Errors occuring in:
- Stem cells (body wide mosaicism)
- Differentiating cells (tissue specific)
- Differentiated cells (organ specific)
Distribution of mosaicism
- Somatic
- Somatic + germline
- Germline (gonadal)
Molecular classes of diseases associated mosaicism
- Mandelian (points mutations)
- Chromosomal / CNV
- Epigenetic
- Mitochondrial
- Complex
Non-pathogenic health impact of mosaicism
- X chromosome inactivation
- Immunogenetic mosaicism
- Complexity of neuronal cell types
Pathogenic health impact of mosaicism
- Disorders exclusively associated with mosaicism (e.g. pallister-killian syndrome)
- Cancer
Cancer cytogenomics
- Key element for diagnosis
- Prognostic value
- Detection of a specific abnormality may define response to therapy
- Monitoring for an early detection of disease relapse or cancer evolution
Cytogenomic mechanisms of cancer
- Chimeric gene fusion with oncogenic properties
- De regulated oncogene expression
- Tumour suppressor gene inactivation
Philadelphia chromosome (Ph’)
Balanced translocation between chromosome 9 and 22, forming the BCR::ABL fusion gene
Clinical implications of Ph’
- Chronic Myeloid Leukaemia (CML)
- Acute Lymphoblastic Leukaemia (ALL)
CML
- Increased incidence >50 years
- 95% Ph’ +ve
- Good prognosis if Ph’+ve
ALL
- Poor prognosis if Ph’+ve
- More common to be Ph’+ve if adult
Transcript common in ALL
e1a2
