G1 control gene status is frequently altered in resectable non-small cell lung cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/94726
Title:
G1 control gene status is frequently altered in resectable non-small cell lung cancer.
Authors:
Betticher, Daniel C; White, Gavin R M; Vonlanthen, S; Liu, X; Kappeler, A; Altermatt, H J; Thatcher, Nick; Heighway, Jim
Abstract:
Progression through the mammalian cell cycle is controlled by a series of cyclins, cyclin-dependent kinases (cdks) and cdk inhibitors. Cyclin D1, cdk4 and the tumour suppressors p16 and retinoblastoma protein (pRb) are thought to comprise a linked system governing cell passage through the G1 phase of the cell cycle. Extending an earlier study on cyclin D1 expression, a series of resectable non-small cell lung carcinomas (NSCLCs) was examined for defects in other elements of this control system. Forty-six of fifty-one NSCLC specimens exhibited at least one alteration of these cell-cycle regulators. Immunohistochemical analysis revealed that 33% and 47% of the tumours failed to express pRb and p16, respectively. Failure to detect pRb did not correlate with loss of heterozygosity at the RB1 locus. Eleven of 12 tumours showing positive (normal) pRb staining over-expressed nuclear localised cyclin D1, including 8 with amplification of the cyclin D1 gene (CCNDI). However, in a number of lesions (n = 5) where cyclin D1 was over-expressed but localised to the cytoplasm, pRb expression was undetectable. Sequencing of exons 1 and 2 of the p16 gene (CDKN2) revealed 3/51 tumours with somatic mutations (in addition to 1 case with a germ-line alteration). All of these lesions were positive for p16 protein. No clear homozygous deletions of CDKN2 were observed by multiplex PCR. As assessed by immunostaining using a p16 monoclonal antibody, there was an inverse correlation of pRb and p16 down-regulation. Whilst patients with tumours over-expressing cyclin D1 had a significantly lower incidence of local relapse, the group whose tumours failed to express pRb had a significantly greater risk of local relapse and tended to have shortened event-free survival. Our data show that alteration of at least one cell cycle-regulator gene occurs in the majority of resectable NSCLCs.
Affiliation:
Institute of Medical Oncology, Inselspital, University of Bern, Switzerland.
Citation:
G1 control gene status is frequently altered in resectable non-small cell lung cancer. 1997, 74 (5):556-62 Int. J. Cancer
Journal:
International Journal of Cancer.
Issue Date:
21-Oct-1997
URI:
http://hdl.handle.net/10541/94726
PubMed ID:
9355981
Type:
Article
Language:
en
ISSN:
0020-7136
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBetticher, Daniel Cen
dc.contributor.authorWhite, Gavin R Men
dc.contributor.authorVonlanthen, Sen
dc.contributor.authorLiu, Xen
dc.contributor.authorKappeler, Aen
dc.contributor.authorAltermatt, H Jen
dc.contributor.authorThatcher, Nicken
dc.contributor.authorHeighway, Jimen
dc.date.accessioned2010-03-23T16:25:46Z-
dc.date.available2010-03-23T16:25:46Z-
dc.date.issued1997-10-21-
dc.identifier.citationG1 control gene status is frequently altered in resectable non-small cell lung cancer. 1997, 74 (5):556-62 Int. J. Canceren
dc.identifier.issn0020-7136-
dc.identifier.pmid9355981-
dc.identifier.urihttp://hdl.handle.net/10541/94726-
dc.description.abstractProgression through the mammalian cell cycle is controlled by a series of cyclins, cyclin-dependent kinases (cdks) and cdk inhibitors. Cyclin D1, cdk4 and the tumour suppressors p16 and retinoblastoma protein (pRb) are thought to comprise a linked system governing cell passage through the G1 phase of the cell cycle. Extending an earlier study on cyclin D1 expression, a series of resectable non-small cell lung carcinomas (NSCLCs) was examined for defects in other elements of this control system. Forty-six of fifty-one NSCLC specimens exhibited at least one alteration of these cell-cycle regulators. Immunohistochemical analysis revealed that 33% and 47% of the tumours failed to express pRb and p16, respectively. Failure to detect pRb did not correlate with loss of heterozygosity at the RB1 locus. Eleven of 12 tumours showing positive (normal) pRb staining over-expressed nuclear localised cyclin D1, including 8 with amplification of the cyclin D1 gene (CCNDI). However, in a number of lesions (n = 5) where cyclin D1 was over-expressed but localised to the cytoplasm, pRb expression was undetectable. Sequencing of exons 1 and 2 of the p16 gene (CDKN2) revealed 3/51 tumours with somatic mutations (in addition to 1 case with a germ-line alteration). All of these lesions were positive for p16 protein. No clear homozygous deletions of CDKN2 were observed by multiplex PCR. As assessed by immunostaining using a p16 monoclonal antibody, there was an inverse correlation of pRb and p16 down-regulation. Whilst patients with tumours over-expressing cyclin D1 had a significantly lower incidence of local relapse, the group whose tumours failed to express pRb had a significantly greater risk of local relapse and tended to have shortened event-free survival. Our data show that alteration of at least one cell cycle-regulator gene occurs in the majority of resectable NSCLCs.en
dc.language.isoenen
dc.subjectLung Canceren
dc.subject.meshAged-
dc.subject.meshCarcinoma, Non-Small-Cell Lung-
dc.subject.meshDNA Methylation-
dc.subject.meshDown-Regulation-
dc.subject.meshExons-
dc.subject.meshFemale-
dc.subject.meshG1 Phase-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshGenes, Retinoblastoma-
dc.subject.meshGenes, p16-
dc.subject.meshHumans-
dc.subject.meshLoss of Heterozygosity-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMutation-
dc.subject.meshPolymerase Chain Reaction-
dc.subject.meshRetinoblastoma Protein-
dc.titleG1 control gene status is frequently altered in resectable non-small cell lung cancer.en
dc.typeArticleen
dc.contributor.departmentInstitute of Medical Oncology, Inselspital, University of Bern, Switzerland.en
dc.identifier.journalInternational Journal of Cancer.en

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.