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. 2011 Jul 1;17(13):4245-53.
doi: 10.1158/1078-0432.CCR-11-0395. Epub 2011 May 11.

Primary central nervous system lymphomas: a validation study of array-based comparative genomic hybridization in formalin-fixed paraffin-embedded tumor specimens

Esteban Braggio  1 , Ellen Remstein McPhail, William Macon, M Beatriz Lopes, David Schiff, Mark Law, Stephanie Fink, Debra Sprau, Caterina Giannini, Ahmet Dogan, Rafael Fonseca, Brian Patrick O'Neill
Affiliations

Primary central nervous system lymphomas: a validation study of array-based comparative genomic hybridization in formalin-fixed paraffin-embedded tumor specimens

Esteban Braggio et al. Clin Cancer Res. .

Abstract

Purpose: Only a limited number of genetic studies have been conducted in primary central nervous system lymphomas (PCNSL), partly due to the rarity of the tumors and the very limited amount of available tissue. In this report, we present the first molecular characterization of copy number abnormalities (CNA) of newly diagnosed PCNSL by array-based comparative genomic hybridization (aCGH) in formalin-fixed paraffin-embedded (FFPE) specimens and compare the results with matched, frozen tumor specimens.

Experimental design: We conducted aCGH in FFPE tissues from PCNSL. Results were compared with matched, paired, frozen tumors.

Results: Our analysis confirmed the good to fair quality and reliability of the data generated from limited amounts of tumoral FFPE tissue. Overall, all PCNSL cases were characterized by highly complex karyotypes, with a median of 23 CNAs per patient (range, 17-47). Overall, 20 chromosomal regions were recurrently found in more than 40% of cases. Deletions of 6p21, 6q, and 9p21.3 and gain of 12q12-q24.33 were the commonest CNAs. Other minimal affected regions were defined, and novel recurrent CNAs affecting single genes were identified in 3q26.32 (TBL1XR1) and 8q12.1 (TOX).

Conclusions: The results obtained are encouraging. Larger archival tissue collections can now be analyzed to complement the still fragmented knowledge we have of the genetic basis of the PCNSL.

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Figures

Figure 1
Figure 1
A) Assay quality comparison between matched paired FFPE and snap-frozen samples. Case A was only analyzed from snap-frozen sample. B) Correlation between assay quality (DLRSpread used as a surrogate) and the CNA concordance level between matched paired FFPE-snap frozen samples. DLRSpread values bellow 0.2 correspond to excellent quality assays; values between 0.2 and 0.3 correspond to good quality; and values above 0.3 are considered marginal. C) The concordance of CNA detection between paired samples increases with the size of the abnormalities; D) Graph showing that higher quality assay was associated with higher concordance of CNA breakpoint location between paired samples.
Figure 2
Figure 2
Overview of copy-number abnormalities identified in this study. Bars at the left of the chromosomes represent losses and bars at the right represent gains. The amplitude of the bars denotes the frequency in which each region was affected.
Figure 3
Figure 3
Overview of 6q status. The 3 most commonly deleted regions (MDR1-MDR3) are highlighted. None of them includes PTPRK (solid line).
See this image and copyright information in PMC

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