What is passenger gene
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Passenger’ mutations are assumed to have neutral impact on cell phenotype. For each individual, or patient, they can arise at any time in the antecedent life history of any cell 5, including a cancer cell lineage. Or they may be a product of genomic instability and/or aetiological exposures causally linked to the cancer 6. They usually register in genomic screens as idiosyncratic, patient and clone-specific mutations and the fact that they can show up in most cells or in dominant clones is no reflection of their impact.
That much is, in principle, clear and reasonable enough. The trouble is these definitions can encourage us to adopt a gene-centric perspective – appearing to imply that having a particular function is an intrinsic or autonomous property of a mutation when this is far from certain. Rather we should assume that mutations arise more or less randomly with respect to any functional effect they may have on a target gene or cellular process. For those that have the potential to alter gene regulation or exome encoded structure, the functional impact they actually have will depend on several factors:
• The cell type involved and its phenotypic response to the mutation. Some oncogenic mutations such as RAS are broad spectrum, impacting on many cellular processes or cell types. Others (e.g. fusion genes) are more cell-type restricted, possibly because they are selectively expressed and often encode transcription factors impacting on cell lineage-specific differentiation programmes 7.
• Cancers develop within a dynamic local ecosystem. In this context, the local adaptive landscape and presence or absence of particular selective pressures may determine whether or not a mutation actually exercises a fitness advantage, i.e. that it is adaptive. An obvious example of this would be a mutation that confers drug resistance. As with antibiotic resistance in bacteria 8, such mutations will arise independently to, and prior to, drug exposure but are only functionally relevant when and if the clone carrying the mutation is exposed to the relevant drug. Even the most frequent oncogene mutations – in p53, will be active and functionally relevant only in the presence of stress signals that co-opt p53 function. Conversely, a ‘driver’ mutation, though persistently present, could become functionally redundant or insignificant (vestigial) under altered selective conditions.
That much is, in principle, clear and reasonable enough. The trouble is these definitions can encourage us to adopt a gene-centric perspective – appearing to imply that having a particular function is an intrinsic or autonomous property of a mutation when this is far from certain. Rather we should assume that mutations arise more or less randomly with respect to any functional effect they may have on a target gene or cellular process. For those that have the potential to alter gene regulation or exome encoded structure, the functional impact they actually have will depend on several factors:
• The cell type involved and its phenotypic response to the mutation. Some oncogenic mutations such as RAS are broad spectrum, impacting on many cellular processes or cell types. Others (e.g. fusion genes) are more cell-type restricted, possibly because they are selectively expressed and often encode transcription factors impacting on cell lineage-specific differentiation programmes 7.
• Cancers develop within a dynamic local ecosystem. In this context, the local adaptive landscape and presence or absence of particular selective pressures may determine whether or not a mutation actually exercises a fitness advantage, i.e. that it is adaptive. An obvious example of this would be a mutation that confers drug resistance. As with antibiotic resistance in bacteria 8, such mutations will arise independently to, and prior to, drug exposure but are only functionally relevant when and if the clone carrying the mutation is exposed to the relevant drug. Even the most frequent oncogene mutations – in p53, will be active and functionally relevant only in the presence of stress signals that co-opt p53 function. Conversely, a ‘driver’ mutation, though persistently present, could become functionally redundant or insignificant (vestigial) under altered selective conditions.
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those characteristics which transfer by other person not a parents by seeing or personally contacts
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