The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin.

Hdl Handle:
http://hdl.handle.net/10147/143796
Title:
The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin.
Authors:
Flanagan, Annabelle M; Rafferty, Gerard; O'Neill, Anne; Rynne, Leonie; Kelly, Jack; McCann, Jack; Carty, Michael P
Affiliation:
Department of Biochemistry, National University of Ireland, Galway, Ireland.
Citation:
The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin. 2007, 19 (4):589-96 Int. J. Mol. Med.
Journal:
International journal of molecular medicine
Issue Date:
Apr-2007
URI:
http://hdl.handle.net/10147/143796
PubMed ID:
17334634
Additional Links:
http://www.spandidos-publications.com/ijmm/19/4/589
Abstract:
Skin cancer, the most common cancer in the general population, is strongly associated with exposure to the ultraviolet component of sunlight. To investigate the relationship between DNA damage processing and skin tumour development, we determined the POLH status of a cohort of skin cancer patients. The human POLH gene encodes DNA polymerase eta (poleta), which normally carries out accurate translesion synthesis past the major UV-induced photoproduct, the dithymine cyclobutane dimer. In the absence of active poleta in xeroderma pigmentosum variant (XPV) patients, mutations accumulate at sites of UV-induced DNA damage, providing the initiating step in skin carcinogenesis. Forty patients diagnosed with skin cancer were genotyped for polymorphisms in the POLH protein-coding sequence, using glycosylase-mediated polymorphism detection (GMPD) and direct DNA sequencing of POLH PCR products derived from white blood cell genomic DNA. All individuals carried the wild-type POLH sequence. No POLH mutations were identified in genomic DNA from skin tumours derived from 15 of these patients. As determined by RT-PCR, POLH mRNA was expressed in all normal and skin tumour tissue examined. Poleta protein was also detectable by Western blotting, in two matched normal and skin tumour extracts. An alternatively spliced form of POLH mRNA, lacking exon 2, was more readily detected in skin tissue than in white blood cells from the same patient. Real-time PCR was used to quantify POLH expression in matched normal and skin tumour-derived mRNA from a series of patients diagnosed with either basal or squamous cell carcinoma. Compared to matched normal skin tissue from the same patient, 1 of 7 SCC, and 4 of 10 BCC tumours examined showed at least a 2-fold reduction in POLH expression, while 1 of 7 SCC, and 3 of 10 BCC tumours showed at least a 2-fold increase in POLH expression. Differences in gene expression, rather than sequence changes may be the main mechanism by which POLH status varies between normal and skin tumours in the population under investigation. Knowledge of the POLH status in skin tumours could contribute to an understanding of the role of this gene in the development of the most common cancer in the general population.
Item Type:
Article
Language:
en
Description:
Skin cancer, the most common cancer in the general population, is strongly associated with exposure to the ultraviolet component of sunlight. To investigate the relationship between DNA damage processing and skin tumour development, we determined the POLH status of a cohort of skin cancer patients. The human POLH gene encodes DNA polymerase eta (poleta), which normally carries out accurate translesion synthesis past the major UV-induced photoproduct, the dithymine cyclobutane dimer. In the absence of active poleta in xeroderma pigmentosum variant (XPV) patients, mutations accumulate at sites of UV-induced DNA damage, providing the initiating step in skin carcinogenesis. Forty patients diagnosed with skin cancer were genotyped for polymorphisms in the POLH protein-coding sequence, using glycosylase-mediated polymorphism detection (GMPD) and direct DNA sequencing of POLH PCR products derived from white blood cell genomic DNA. All individuals carried the wild-type POLH sequence. No POLH mutations were identified in genomic DNA from skin tumours derived from 15 of these patients. As determined by RT-PCR, POLH mRNA was expressed in all normal and skin tumour tissue examined. Poleta protein was also detectable by Western blotting, in two matched normal and skin tumour extracts. An alternatively spliced form of POLH mRNA, lacking exon 2, was more readily detected in skin tissue than in white blood cells from the same patient. Real-time PCR was used to quantify POLH expression in matched normal and skin tumour-derived mRNA from a series of patients diagnosed with either basal or squamous cell carcinoma. Compared to matched normal skin tissue from the same patient, 1 of 7 SCC, and 4 of 10 BCC tumours examined showed at least a 2-fold reduction in POLH expression, while 1 of 7 SCC, and 3 of 10 BCC tumours showed at least a 2-fold increase in POLH expression. Differences in gene expression, rather than sequence changes may be the main mechanism by which POLH status varies between normal and skin tumours in the population under investigation. Knowledge of the POLH status in skin tumours could contribute to an understanding of the role of this gene in the development of the most common cancer in the general population.
MeSH:
Aged; Aged, 80 and over; Alternative Splicing; Base Sequence; Carcinoma, Squamous Cell; Cohort Studies; DNA-Directed DNA Polymerase; Female; Gene Expression; Humans; Male; Middle Aged; Molecular Sequence Data; Mutation; Polymorphism, Genetic; RNA, Messenger; Sequence Analysis, DNA; Skin Neoplasms
ISSN:
1107-3756

Full metadata record

DC FieldValue Language
dc.contributor.authorFlanagan, Annabelle Men
dc.contributor.authorRafferty, Gerarden
dc.contributor.authorO'Neill, Anneen
dc.contributor.authorRynne, Leonieen
dc.contributor.authorKelly, Jacken
dc.contributor.authorMcCann, Jacken
dc.contributor.authorCarty, Michael Pen
dc.date.accessioned2011-10-03T14:28:58Z-
dc.date.available2011-10-03T14:28:58Z-
dc.date.issued2007-04-
dc.identifier.citationThe human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin. 2007, 19 (4):589-96 Int. J. Mol. Med.en
dc.identifier.issn1107-3756-
dc.identifier.pmid17334634-
dc.identifier.urihttp://hdl.handle.net/10147/143796-
dc.descriptionSkin cancer, the most common cancer in the general population, is strongly associated with exposure to the ultraviolet component of sunlight. To investigate the relationship between DNA damage processing and skin tumour development, we determined the POLH status of a cohort of skin cancer patients. The human POLH gene encodes DNA polymerase eta (poleta), which normally carries out accurate translesion synthesis past the major UV-induced photoproduct, the dithymine cyclobutane dimer. In the absence of active poleta in xeroderma pigmentosum variant (XPV) patients, mutations accumulate at sites of UV-induced DNA damage, providing the initiating step in skin carcinogenesis. Forty patients diagnosed with skin cancer were genotyped for polymorphisms in the POLH protein-coding sequence, using glycosylase-mediated polymorphism detection (GMPD) and direct DNA sequencing of POLH PCR products derived from white blood cell genomic DNA. All individuals carried the wild-type POLH sequence. No POLH mutations were identified in genomic DNA from skin tumours derived from 15 of these patients. As determined by RT-PCR, POLH mRNA was expressed in all normal and skin tumour tissue examined. Poleta protein was also detectable by Western blotting, in two matched normal and skin tumour extracts. An alternatively spliced form of POLH mRNA, lacking exon 2, was more readily detected in skin tissue than in white blood cells from the same patient. Real-time PCR was used to quantify POLH expression in matched normal and skin tumour-derived mRNA from a series of patients diagnosed with either basal or squamous cell carcinoma. Compared to matched normal skin tissue from the same patient, 1 of 7 SCC, and 4 of 10 BCC tumours examined showed at least a 2-fold reduction in POLH expression, while 1 of 7 SCC, and 3 of 10 BCC tumours showed at least a 2-fold increase in POLH expression. Differences in gene expression, rather than sequence changes may be the main mechanism by which POLH status varies between normal and skin tumours in the population under investigation. Knowledge of the POLH status in skin tumours could contribute to an understanding of the role of this gene in the development of the most common cancer in the general population.en
dc.description.abstractSkin cancer, the most common cancer in the general population, is strongly associated with exposure to the ultraviolet component of sunlight. To investigate the relationship between DNA damage processing and skin tumour development, we determined the POLH status of a cohort of skin cancer patients. The human POLH gene encodes DNA polymerase eta (poleta), which normally carries out accurate translesion synthesis past the major UV-induced photoproduct, the dithymine cyclobutane dimer. In the absence of active poleta in xeroderma pigmentosum variant (XPV) patients, mutations accumulate at sites of UV-induced DNA damage, providing the initiating step in skin carcinogenesis. Forty patients diagnosed with skin cancer were genotyped for polymorphisms in the POLH protein-coding sequence, using glycosylase-mediated polymorphism detection (GMPD) and direct DNA sequencing of POLH PCR products derived from white blood cell genomic DNA. All individuals carried the wild-type POLH sequence. No POLH mutations were identified in genomic DNA from skin tumours derived from 15 of these patients. As determined by RT-PCR, POLH mRNA was expressed in all normal and skin tumour tissue examined. Poleta protein was also detectable by Western blotting, in two matched normal and skin tumour extracts. An alternatively spliced form of POLH mRNA, lacking exon 2, was more readily detected in skin tissue than in white blood cells from the same patient. Real-time PCR was used to quantify POLH expression in matched normal and skin tumour-derived mRNA from a series of patients diagnosed with either basal or squamous cell carcinoma. Compared to matched normal skin tissue from the same patient, 1 of 7 SCC, and 4 of 10 BCC tumours examined showed at least a 2-fold reduction in POLH expression, while 1 of 7 SCC, and 3 of 10 BCC tumours showed at least a 2-fold increase in POLH expression. Differences in gene expression, rather than sequence changes may be the main mechanism by which POLH status varies between normal and skin tumours in the population under investigation. Knowledge of the POLH status in skin tumours could contribute to an understanding of the role of this gene in the development of the most common cancer in the general population.-
dc.language.isoenen
dc.relation.urlhttp://www.spandidos-publications.com/ijmm/19/4/589en
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAlternative Splicing-
dc.subject.meshBase Sequence-
dc.subject.meshCarcinoma, Squamous Cell-
dc.subject.meshCohort Studies-
dc.subject.meshDNA-Directed DNA Polymerase-
dc.subject.meshFemale-
dc.subject.meshGene Expression-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMutation-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshRNA, Messenger-
dc.subject.meshSequence Analysis, DNA-
dc.subject.meshSkin Neoplasms-
dc.titleThe human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry, National University of Ireland, Galway, Ireland.en
dc.identifier.journalInternational journal of molecular medicineen
dc.description.provinceConnacht-

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