Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease

dc.contributor.authorBehrens, C
dc.contributor.authorTravis, LB
dc.contributor.authorWistuba, II
dc.contributor.authorDavis, S
dc.contributor.authorMaitra, A
dc.contributor.authorClarke, EA
dc.contributor.authorLynch, CF
dc.contributor.authorGlimelius, B
dc.contributor.authorWiklund, T
dc.contributor.authorTarone, R
dc.contributor.authorGazdar, AF
dc.date.accessioned2025-01-21T01:31:10Z
dc.date.available2025-01-21T01:31:10Z
dc.date.issued2000
dc.description.abstractThe risk of lung and breast cancer is significantly increased after therapy for Hodgkin's disease (HD), but there are few data that describe the molecular profiles of these tumors. We investigated the genetic abnormalities in second primary lung (n = 19) and breast cancers (n = 19) that follow therapy for HD ("post-HD cancers") and compared these with changes observed in corresponding tumor types (57 lung and 20 breast cancers) arising in the general population ("sporadic cancers"). DNA obtained from archival tissues was examined using PCR-based analyses for loss of heterozygosity and microsatellite alterations (MAs) at several chromosomal regions, TP53 and K-uas gene mutations, and frameshift mutations at minisatellite sequences at the coding regions of several genes (TGF-beta RII, IGFIIR, BAX, hMSH6, and hMSH3). The occurrence of loss of heterozygosity at all chromosomal regions taken together and frequencies at most individual areas were similar for the post-HD and sporadic cancers for both lung and breast sites, The overall frequency of MAs in the post-HD tumors was substantially greater (lung, 2.4-fold, P = 0.004; breast, 4.2-fold, P = 0.16) than that in the respective sporadic cancers. No differences in the pattern of TP53 and K-ras mutations were detected between post-HD and sporadic cancers. No mutations were detected at the minisatellite sequences examined. MAs, which reflect widespread genomic instability, occur at greatly increased frequency in post-HD lung and breast cancers. Although the mechanisms underlying the development of increased MAs are unknown, they have been associated with immunosuppression and radiation exposure. Future research should address the role that MAs, as well as other influences, may play in the development of neoplasias that occur after therapy for HD.
dc.description.funderNCI NIH HHS
dc.fuente.origenWOS
dc.identifier.issn1055-9965
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96999
dc.identifier.wosidWOS:000089909300004
dc.issue.numero10
dc.language.isoen
dc.pagina.final1035
dc.pagina.inicio1027
dc.revistaCancer epidemiology biomarkers & prevention
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleMolecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease
dc.typeartículo
dc.volumen9
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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