title: Genomic alterations reveal potential for higher grade transformation in follicular lymphoma and confirm parallel evolution of tumor cell clones.
abstract: Our aim was to examine the genetics of clonal evolution in follicular lymphoma (FL) and to identify genetic alterations associated with disease progression. A total of 100 biopsies from 44 patients diagnosed with t(14;18)-positive FL were examined by array comparative genomic hybridization. In 20 patients the patterns of somatic hypermutations (SHMs) in the variable region of heavy chain gene were additionally analyzed. Gain of chromosome X in male samples was a marker for poor outcome (P < .01). Gains involving chromosome 2, 3q, and 5 were exclusively present in FL biopsies from cases with higher grade transformation and were among the copy number alterations (CNAs) associated with inferior survival. Although we noted a trend for increasing genomic complexity in initial versus late FL samples, the overall frequencies of CNAs in initial and late FL biopsies showed a surprisingly stable pattern through the course of the disease. In 27 of cases the initial samples harbored CNAs that were absent in relapse samples, indicating that tumor cell clones at relapse were not direct descendants of initially dominating clones. The pattern of SHMs confirmed parallel development of tumor cell clones in 14 cases. Our findings support the hypothesis of common progenitor cells in FL.
authors.affiliation: Centre for Cancer Biomedicine, University of Oslo, Norway. marianne.brodtkorb.eide@rr-research.no
authors.forename: Marianne Brodtkorb
authors.initials: MB
authors.lastname: Eide
authors.forename: Knut
authors.initials: K
authors.lastname: Liestøl
authors.forename: Ole Christian
authors.initials: OC
authors.lastname: Lingjaerde
authors.forename: Marit E
authors.initials: ME
authors.lastname: Hystad
authors.forename: Stine H
authors.initials: SH
authors.lastname: Kresse
authors.forename: Leonardo
authors.initials: L
authors.lastname: Meza-Zepeda
authors.forename: Ola
authors.initials: O
authors.lastname: Myklebost
authors.forename: Gunhild
authors.initials: G
authors.lastname: Trøen
authors.forename: Hege Vangstein
authors.initials: HV
authors.lastname: Aamot
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Erlend Bremertun
authors.initials: EB
authors.lastname: Smeland
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002999:Clone Cells / Q000473:pathology*; D055028:Comparative Genomic Hybridization; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015996:Survival Rate; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region