A review on tumor heterogeneity and evolution in multiple myeloma: pathological, radiological, molecular genetics, and clinical integration

Schürch, Christian M.; Rasche, Leo; Frauenfeld, Leonie; Weinhold, Niels; Fend, Falko (2020). A review on tumor heterogeneity and evolution in multiple myeloma: pathological, radiological, molecular genetics, and clinical integration. Virchows Archiv, 476(3), pp. 337-351. Springer 10.1007/s00428-019-02725-3

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Recent research has dramatically advanced our understanding of the genetic basis of multiple myeloma (MM). MM displays enormous inter- and intratumoral heterogeneity, and underlies a clonal evolutionary process driven and shaped by diverse factors such as clonal competition, tumor microenvironment, host immunity, and therapy. Two main cytogenetic groups are distinguished: MM with recurrent translocations involving the immunoglobulin heavy chain locus and MM with hyperdiploidy involving the odd chromosomes. The disease virtually always starts with a preneoplastic prodromal phase-monoclonal gammopathy of undetermined significance-that variably progresses to symptomatic MM within a few months or many years. Tumor heterogeneity and its evolution in space and time have important consequences for the clinical management and outcome of MM patients. At diagnosis, spatial intratumoral heterogeneity poses a challenge for classification and risk stratification. During maintenance therapy, clonal evolution may complicate disease monitoring and promote drug resistance. Upon progression or transformation, identifying the dominant disease-driving neoplastic clones and elucidating their properties are key to tailor personalized therapy. In this review, we discuss tumor heterogeneity and clonal evolution in MM, integrating pathological, radiological, molecular genetics, and clinical data. Current and prospective classification schemes and prognostic parameters, incorporating new genetic and proteomic discoveries and advances in imaging, are highlighted. In addition, the roles of the tumor microenvironment, host immunity, and resistance mutations, and their effects on therapy, are discussed. An improved understanding of high-risk disease, tumor heterogeneity, and clonal evolution will guide future therapies and may ultimately lead towards a cure for MM.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

UniBE Contributor:

Schürch, Christian

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0945-6317

Publisher:

Springer

Language:

English

Submitter:

Christian Schürch

Date Deposited:

26 Jun 2020 10:59

Last Modified:

18 Dec 2020 02:30

Publisher DOI:

10.1007/s00428-019-02725-3

PubMed ID:

31848687

BORIS DOI:

10.7892/boris.144622

URI:

https://boris.unibe.ch/id/eprint/144622

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