Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy.

2.50
Hdl Handle:
http://hdl.handle.net/10541/85598
Title:
Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy.
Authors:
Hendry, Jolyon H
Abstract:
PURPOSE: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. RESULTS: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. CONCLUSIONS: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability, particularly gene polymorphisms, or other low penetrant gene mutations, contribute to the recognized spectrum of normal tissue radiosensitivity amongst cancer patients, or in the general population. Tests for such genetic modifications may help in the search for more accurate prognostic markers of response, which hopefully could be used in addition to other strategies to further improve the outcome for cancer patients given radiotherapy.
Affiliation:
CRC Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, M20 4BX, Manchester, UK.
Citation:
Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy. 2001, 59 (2):117-26 Radiother Oncol
Journal:
Radiotherapy and Oncology
Issue Date:
May-2001
URI:
http://hdl.handle.net/10541/85598
PubMed ID:
11325439
Type:
Article
Language:
en
ISSN:
0167-8140
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHendry, Jolyon Hen
dc.date.accessioned2009-11-06T16:04:24Z-
dc.date.available2009-11-06T16:04:24Z-
dc.date.issued2001-05-
dc.identifier.citationGenomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy. 2001, 59 (2):117-26 Radiother Oncolen
dc.identifier.issn0167-8140-
dc.identifier.pmid11325439-
dc.identifier.urihttp://hdl.handle.net/10541/85598-
dc.description.abstractPURPOSE: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. RESULTS: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. CONCLUSIONS: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability, particularly gene polymorphisms, or other low penetrant gene mutations, contribute to the recognized spectrum of normal tissue radiosensitivity amongst cancer patients, or in the general population. Tests for such genetic modifications may help in the search for more accurate prognostic markers of response, which hopefully could be used in addition to other strategies to further improve the outcome for cancer patients given radiotherapy.en
dc.language.isoenen
dc.subjectRadiation-Induced Canceren
dc.subjectSecond Primary Canceren
dc.subject.meshCell Division-
dc.subject.meshDNA Damage-
dc.subject.meshHumans-
dc.subject.meshMutation-
dc.subject.meshNeoplasms, Radiation-Induced-
dc.subject.meshNeoplasms, Second Primary-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshRadiation Injuries-
dc.subject.meshRadiation Tolerance-
dc.subject.meshStem Cells-
dc.subject.meshWound Healing-
dc.titleGenomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy.en
dc.typeArticleen
dc.contributor.departmentCRC Experimental Radiation Oncology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, M20 4BX, Manchester, UK.en
dc.identifier.journalRadiotherapy and Oncologyen
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