Molecular pathogenesis of non-Hodgkin lymphoma: a clinical perspective.
Despite a common origin from mature lymphoid cells, non-Hodgkin lymphomas (NHL) represent a surprisingly heterogeneous group of lymphoid malignancies whose classification is continuously being remodeled. The most recent proposal, the Revised European-American classification, introduces pathogenetic features among the classification criteria. In this respect, knowledge of the molecular pathogenesis of NHL, which is based upon genetic lesions leading to activation of proto-oncogenes (e.g. BCL-1, BCL-2, BCL-6, c-MYC) or disruption of tumor suppressor genes (e.g. p53), is becoming increasingly relevant for the clinician. These lesions combine into multiple molecular pathways which are selectively associated with distinct NHL types. Thus, for example, rearrangements of BCL-1, BCL-2, BCL-6, and c-MYC ar the genetic hallmarks of mantle cell, follicular, diffuse large cell, and Burkitt's lymphoma, respectively. Overall, from clinical perspective, NHL genetic lesions serve three purposes: a) they assist and complement histologic diagnosis; b) they provide a molecular marker with prognostic relevance; c) they allow evaluation of minimal residual disease through highly specific and highly sensitive technologies.
Gaidano
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Laboratorio di Medicina e Oncologia Molecolare, Ospedale San Luigi Gonzaga, Università di Torino, Orbassano (TO), Italy.
Pastore
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Volpe
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D002472:Cell Transformation, Viral; D002877:Chromosomes, Human / Q000648:ultrastructure; D019938:Cyclin D1; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D006566:Herpesviridae Infections; D004854:Herpesvirus 4, Human; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000235:genetics* / Q000473:pathology / Q000821:virology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D014412:Tumor Virus Infections
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D019938:Cyclin D1