+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Comprehensive analysis of copy number and allele status identifies multiple chromosome defects underlying follicular lymphoma pathogenesis

Comprehensive analysis of copy number and allele status identifies multiple chromosome defects underlying follicular lymphoma pathogenesis

Clinical Cancer Research 13(16): 4777-4785

Follicular lymphoma (FL) constitutes the second most common non-Hodgkin's lymphoma in the Western world. The clinical course is variable and only in part explained by known tumor-intrinsic or -extrinsic factors. FL carries the hallmark chromosomal translocation t(14;18), deregulating the expression of Bcl-2, but this is not sufficient to explain either FL biology or clinical behavior. We have employed high-density genomic profiling technology using the Affymetrix 50K-XbaI oligonucleotide single nucleotide polymorphism-chip platform to interrogate the genomes of 58 fluorescence-activated cell-sorted (FACS) FL specimens for chromosomal copy number changes and 46 specimens for loss of heterozygosity (LOH). We report (a) previously unknown high-frequency copy-neutral LOH (uniparental disomy) in FL on chromosomes 1p (approximately 50%) and 6p (approximately 30%); (b) that del6q is complex, as reported, with at least two regions of minimal common loss at 6q13-15 and 6q23-24, and that in addition, approximately 8% of FL specimens contain a homozygous deletion at 6q23.3-24.1 that spans the negative NFkappaB regulator A20 and the p53 apoptosis effector PERP; (c) that combined analysis of chromosome 17p for LOH, copy number, and p53 mutations shows that most p53 mutations in FL do not involve del17p. Finally, we map high-frequency LOH with and without copy loss on chromosomes 9p, 10q, and 16p and genomic gains on 2p15-16 and 8q24.22-24.3. This comprehensive description of the pathologic anatomy of the FL genome uncovers novel genetic lesions and should aid with identification of genes relevant to FL biology and clinical behavior.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 052269754

Download citation: RISBibTeXText

PMID: 17699855

DOI: 10.1158/1078-0432.ccr-07-0456

Related references

Integrated immunohistochemical and DNA copy number profiling analysis provides insight into the molecular pathogenesis of canine follicular lymphoma. Veterinary and Comparative Oncology 15(3): 852-867, 2017

Comprehensive DNA copy number profiling of meningioma using a chromosome 1 tiling path microarray identifies novel candidate tumor suppressor loci. Cancer Research 65(7): 2653-2661, 2005

Copy number variation analysis on a non-Hodgkin lymphoma case-control study identifies an 11q25 duplication associated with diffuse large B-cell lymphoma. Plos one 9(8): E105382, 2014

High resolution analysis of follicular lymphoma genomes reveals somatic recurrent sites of copy-neutral loss of heterozygosity and copy number alterations that target single genes. Genes Chromosomes and Cancer 49(8): 669-681, 2010

Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients. Journal of Psychiatric Research 44(14): 971-978, 2010

Comprehensive genomic copy number and sequence analysis of 28 chromosome 5q31.2 candidate genes in de novo MDS. 2007

Duodenal follicular lymphoma: comprehensive gene expression analysis with insights into pathogenesis. Cancer Science 105(5): 608-615, 2014

Comprehensive analysis of Copy Number Variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration. Plos one 7(4): E35255, 2012

Identification of chromosomal copy number changes associated with transformation of follicular lymphoma to diffuse large B-cell lymphoma. Human Pathology 34(9): 915-923, 2003

Copy number gain at 12q12-14 may be important in the transformation from follicular lymphoma to diffuse large B cell lymphoma. British Journal of Cancer 84(4): 499-503, 2001

A comparative genomic hybridization of copy number changes in the progression of follicular lymphoma to diffuse large B cell lymphoma. British Journal of Haematology 102(1): 35, 1998

Transformation of follicular lymphoma to diffuse large cell lymphoma is associated with a heterogeneous set of DNA copy number and gene expression alterations. Blood 101(8): 3109-3117, 2003

Applying microsatellite multiplex PCR analysis (MMPA) for determining allele copy-number status and percentage of normal cells within tumors. Plos one 7(8): E42682, 2012

An anonymous human single copy genomic clone, D5S6 (M4) on chromosome 5 identifies a three allele RFLP. Nucleic Acids Research 14(4): 1923, 1986

Allele copy number and underlying pathology are associated with subclinical severity in equine type 1 polysaccharide storage myopathy (PSSM1). Plos one 7(7): E42317, 2012