Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances

Cheung, Katherine; Shah, Sohrab P.; Steidl, Christian; Johnson, Nathalie A.; Relander, Thomas; Telenius, Adèle; Lai, Betty; Murphy, Kevin; Lam, Wan L.; Al-Tourah, Abdulwahab J.; Connors, Joseph M.; Ng, Raymond T.; Gascoyne, Randy D.; Horsman, Douglas E.

doi:10.1182/blood-2008-02-140616

Cited by 122 publications

(103 citation statements)

References 52 publications

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“…When comparing by t(14;18) status, we found that cases lacking t(14;18) showed gains in 1q, 3, 14q, and loss in 6q. Similar to Cheung et al, we did not find gains in 18q in our t(14;18) negative cases [6] but we did find gains in chromosome three similar to Tagawa et al [5]. We also found that extranodal FL cases had significant gains 3p, 4q, 7p, and 17p as compared to nodal FL.…”

supporting

confidence: 89%

“…We found that in low stage FL the most frequent gains are in chromosomes 1, 6p, 7q, 12p, 15q, X, and 17 while the most frequent deletions are in chromosomes 1q, 17q, and X. Comparison of our results with previous study of 127 FL by CGH method shows overall similar results [6]. Notable difference present in stage I FL cases includes gains in 16p and deletions in 17q.…”

supporting

confidence: 84%

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Biological characterization of stage I follicular lymphoma according to extranodal or nodal primary origin and t(14;18) status using high‐resolution array‐based comparative genomic hybridization

Weinberg

Hoppe

et al. 2015

American J Hematol

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Biological characterization of stage I follicular lymphoma according to extranodal or nodal primary origin and t(14;18) status using high-resolution array-based comparative genomic hybridization To the Editor: Follicular lymphoma (FL) is the most frequent indolent lymphoma and has a variable clinical course. Although generally characterized by an indolent clinical behavior, many cases eventually transform to an aggressive large B-cell lymphoma [1]. Although most of the patients have advanced disease at presentation, approximately 10-20% of patients with FL present in limited stages (Stage I-II) [1]. In a retrospective analysis, more than half of patients with early stage FL remained untreated at a median of 6 or more years, and survival was comparable to that observed in patients undergoing immediate treatment [1]. FLs are generally characterized by the presence of the t(14;18)(q32;q21), which causes a fusion of the BCL2 oncogene with the immunoglobulin heavy chain joining region. The IGH/BCL2 rearrangement is a relatively specific molecular marker of FL, frequently used for diagnosis and monitoring of disease [2]. We have recently shown that the incidence of t(14;18) is significantly lower in limited stage FL and the status of t(14;18) appears to be predictive of clinical outcome [2]. Little is known of the molecular genetics of t(14;18)-negative FL or of the genetic differences between nodal and extranodal FL. Tagawa et al. has shown that trisomy 3 is a specific genomic aberration of t(14;18)-negative FL [3]. Leich et al. did not confirm this finding in their comparison of FLs with and without t(14;18) [4]. Katzenberger found that a distinctive subset of t(14;18)-negative nodal FL is characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36 [5]. The goal of the current study was to characterize stage I FL using high resolution array-based comparative genomic hybridization (aCGH). Validation of findings in aCGH were performed on 20 stage I FL as well as an additional 28 stage I and II FL cases by both RNA gene expression and DNA copy number.Twenty stage I FL were identified from the pathology database of Stanford University as previously described [2]. Agilent 60-mer oligonucleotide microarrays were used to analyze DNA copy number variations. FFPE tissue DNA isolation, labeling, and microarray processing and feature extraction were preformed according to the manufacture instructions (Agilent Techologies, Santa Clara, CA). The obtained data was analyzed using both Agilent DNA Analytics 4.0 Software and CGH-miner (Stanford, CA) software. Only gains and losses identified by both methods were considered significant. Cases were compared both by origin from extranodal versus nodal site and by t(14;18) status. Genomic DNA was isolated using Ambion-Applied Biosystems (Foster City, CA) total nucleic Acid Isolation Kit. Multiplex PCR were performed on an ABI 7900HT PCR systems. RNA were isolated according to Ambion-Applied Biosystems. GAPDH was used as the reference gene. PCR we...

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supporting

confidence: 89%

supporting

confidence: 84%

Biological characterization of stage I follicular lymphoma according to extranodal or nodal primary origin and t(14;18) status using high‐resolution array‐based comparative genomic hybridization

Weinberg

Hoppe

et al. 2015

American J Hematol

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“…Surprisingly, even the degraded archival Pap smear DNAs showed similar structural aberrations as matched DQ samples on Agilent array CGH and Infinium SNP arrays, although with greater background noise. One low-grade follicular lymphoma aspirate clearly manifested (Figure 2A) recentlydescribed poor-prognostic genomic copy number features, 11 while some samples of SCLC showed ( Figure 2B) 18q amplification encompassing BCL-2, an aberration correlated with responsiveness to certain antitumor drugs. 12 Positive identification of gross genomic structural defects in whole slide scrapes of FNAC samples is remarkable, given the potential a priori for low tumor cellular fraction in aspirates.…”

Section: Discussionmentioning

confidence: 99%

Archival Fine-Needle Aspiration Cytopathology (FNAC) Samples

Killian

Walker

Suuriniemi

et al. 2010

The Journal of Molecular Diagnostics

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Microarray technologies provide high-resolution maps of chromosome imbalances and epigenomic aberrations in the cancer cell genome. Such assays are often sensitive to sample DNA integrity , voiding the utility of many archival pathology specimens and necessitating the special handling of prospective clinical specimens. We have identified the remarkable preservation of higher-molecular weight DNA in archival fine-needle aspiration cytopathology specimens from patients greater than 10 years of age. We further demonstrate the outstanding technical performance of 57 fine-needle aspiration cytopathology samples for aberration detection on high-resolution comparative genomic hybridization array , DNA methylation , and single nucleotide polymorphism genotyping platforms. Forty-four of 46 malignant aspirates in this study manifested unequivocal genomic aberrations. Importantly , matched Papanicolaou and Diff-Quik fine-needle aspiration cytopathology samples showed critical differences in DNA preservation and DNA integrity. Overall , this study identifies a largely untapped reserve of human pathology specimens for molecular profil- The two most common modalities for collecting patient tissue samples for pathological analysis can be roughly divided into surgical and cytologic. The former includes core needle and surgical biopsy, and these are typically processed as formalin-fixed, paraffin-embedded (FFPE) samples. FFPE surgical pathology specimens currently comprise the foundation for retrospective clinical genetic profiling studies, and also are typically required for prospective patient enrollment in clinical trials. Alternatively, fine-needle aspiration cytology (FNAC) procedures may be used for rapid, cost-effective and accurate diagnosis with reduced patient morbidity.1 Common anatomical sources for diagnostic FNAC specimens include breast, thyroid, lymph nodes, thoracic and visceral organs, and deep soft tissues. FNAC samples may be the only archival materials for certain diagnoses such as small cell lung cancer (SCLC). Body fluids and epithelial scrapes are another source of cytology preparation, including pleural effusion, ascitic fluid, cerebral-spinal fluid, cervical Papsmears, and bronchial and esophageal brushings. Overall, cytologic preparations represent an estimated 10 to 20% of archival hospital pathology specimens, and may be significantly enriched for particular pathological diagnoses.We recently reported the excellent performance of archival FFPE samples for large-scale molecular profiling using the GoldenGate methylation assay, a modest-density bisulfite genotyping platform.2 However, the more-informative, higher-resolution genotyping arrays for tissue molecular profiling require DNA of higher molecular weight than is often retrieved from archival FFPE samples, because of requirements for unbiased whole genome amplification, which is compromised in FFPE samples over time. Thus, array-

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“…This comprised the detection of other recurrent genomic structural aberrations including the loss of 4q34-q35, gain of 3p, 3q, and 12q, all of which can be seen in conventional follicular lymphoma, [23][24][25][26] but are detected at higher frequencies in nodal marginal zone lymphomas. 27,28 Gains of 2p (four cases with three as focal gains of REL, at higher frequency than observed in follicular lymphoma), 9q, and 11p were also recurrently observed.…”

Section: Modern Pathology (2016) 29 570-581mentioning

confidence: 99%

Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations

et al. 2016

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A predominantly diffuse growth pattern and CD23 co-expression are uncommon findings in nodal follicular lymphoma and can create diagnostic challenges. A single case series in 2009 (Katzenberger et al) proposed a unique morphologic variant of nodal follicular lymphoma, characterized by a predominantly diffuse architecture, lack of the t(14;18) IGH/BCL2 translocation, presence of 1p36 deletion, frequent inguinal lymph node involvement, CD23 co-expression, and low clinical stage. Other studies on CD23+ follicular lymphoma, while associating inguinal location, have not specifically described this architecture. In addition, no follow-up studies have correlated the histopathologic and cytogenetic/molecular features of these cases, and they remain a diagnostic problem. We identified 11 cases of diffuse, CD23+ follicular lymphoma with histopathologic features similar to those described by Katzenberger et al. Along with pertinent clinical information, we detail their histopathology, IGH/BCL2 translocation status, lymphoma-associated chromosomal gains/losses, and assessment of mutations in 220 lymphoma-associated genes by massively parallel sequencing. All cases showed a diffuse growth pattern around well-to ill-defined residual germinal centers, uniform CD23 expression, mixed centrocytic/centroblastic cytology, and expression of at least one germinal center marker. Ten of 11 involved inguinal lymph nodes, 5 solely. By fluorescence in situ hybridization analysis, the vast majority lacked IGH/BCL2 translocation (9/11). Deletion of 1p36 was observed in five cases and included TNFRSF14. Of the six cases lacking 1p36 deletion, TNFRSF14 mutations were identified in three, highlighting the strong association of 1p36/ TNFRSF14 abnormalities with this follicular lymphoma variant. In addition, 9 of the 11 cases tested (82%) had STAT6 mutations and nuclear P-STAT6 expression was detectable in the mutated cases by immunohistochemistry. The proportion of STAT6 mutations is higher than recently reported in conventional follicular lymphoma (11%). These findings lend support for a clinicopathologic variant of t(14;18) negative nodal follicular lymphoma and suggests importance of the interleukin (IL)-4/JAK/STAT6 pathway in this variant.

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Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances

Abstract: The secondary genetic events associated with follicular lymphoma (FL) progression are not well defined. We applied genome-wide BAC array comparative genomic hybridization to 106 diagnostic biopsies of FL to characterize regional genomic imbalances. Using

Cited by 122 publications

References 52 publications

Biological characterization of stage I follicular lymphoma according to extranodal or nodal primary origin and t(14;18) status using high‐resolution array‐based comparative genomic hybridization

Biological characterization of stage I follicular lymphoma according to extranodal or nodal primary origin and t(14;18) status using high‐resolution array‐based comparative genomic hybridization

Archival Fine-Needle Aspiration Cytopathology (FNAC) Samples

Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations

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