Deletion of chromosome bands 11q22-q23 in lymphoproliferative disorders and the genetics of mantle cell lymphoma

8.1 Deletion in chromosome bands 11q22-q23 in mantle cell lymphoma (study I) ....... 44 8.2 Discontinuous deletion in 11q23 in chronic lymphocytic leukemia (study II). Franssila K, Knuutila S. Gene expression profiling in mantle cell lymphoma and its blastoid variant. Submitted. The publications are referred to by their Roman numerals in the text. 6 2 ABBREVIATIONS BAC bacteria artificial chromosome CLL chronic lymphocytic leukemia cDNA complementary deoxyribonucleic acid CGH comparative genomic hybridization DAPI 4', 6-diamidino-2-phenylindole dATP deoxyadenosine triphosphate dCTP deoxycytidine triphosphate DLBCL diffuse large B-cell lymphoma DNA deoxyribonucleic acid dUTP deoxyuridine triphosphate FISH fluorescence in situ hybridization FITC fluorescein-isothiocyanate FL follicular lymphoma HL Hodgkin lymphoma kb kilobase kD kilodalton LOH loss of heterozygosity MALT mucosa-associated lymphoid tissue Mb megabase MCL mantle cell lymphoma mRNA messenger ribonucleic acid MSC mechanically stretched chromosome NHL non-Hodgkin's lymphoma NK natural killer p chromosome short arm PAC P1 artificial chromosome PAGE polyacrylamide gel electrophoresis PCA principal component analysis PCR polymerase chain reaction PGL paraganglioma q chromosome long arm RNA ribonucleic acid REAL A revised European-American classification for lymphoid neoplasms RT-PCR reverse transcription polymerase chain reaction SDS sodium dodecyl sulfate SLL small lymphocytic lymphoma SSC standard saline citrate SSCP single strand conformation polymorphism TBE Tris-borate/EDTA electrophoresis buffer TRITC tetra-rhodamine-isothiocyanate WHO World Health Organization YAC yeast artificial chromosome 7 3 ABSTRACT Chromosome bands 11q22-q23 have been found frequently deleted in a number of solid tumors and lymphoproliferative disorders, suggesting the existence of tumor suppressor gene(s) in this area. This abnormality has been found in mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) by comparative genomic hybridization studies (Karhu et al., 1997; Monni et al., 1998). By using the samples from MCL and CLL patients, we wanted to identify the minimal common region of deletion in 11q22-q23 and the candidate gene in the region. We also wanted to study the occurrence of the deletion in 11q22-q23 in different types of lymphoma. Because MCL is a relatively newly identified disease entity whose molecular background is not well known, it was also our aim to study the gene expression profiles of MCL and its blastoid variant. Altogether we studied samples from 158 lymphoma or leukemia patients. One hundred and fifty-two samples were studied using fluorescence in situ hybridization (FISH) with YAC (yeast artificial chromosome) probes from 11q22.1-q23.3. Two critical regions were identified in 11q22-q23, one represented by YAC755b11 and the other by YAC785e12. The presence of the deletion in …