Genomic Alterations in Blastic Natural Killer/Extranodal Natural Killer-Like T Cell Lymphoma with Cutaneous Involvement

Abstract

Natural killer and natural killer-like T cell lymphomas represent a rare type of non-Hodgkin's lymphoma originally described to involve the upper aerodigestive tract. This malignancy has been increasingly observed in other extranodal sites, particularly in the skin. Patients with cutaneous natural killer cell lymphoma generally have a poor prognosis; however, the etiology and the underlying molecular pathogenesis remain unclear. This study aimed to investigate comprehensively genomic changes in blastic natural killer and extranodal natural killer-like T cell lymphoma with cutaneous involvement. Comparative genomic hybridization showed chromosome imbalances in six of eight cases studied (75%). The mean number of chromosome imbalances per sample was 2.18+/-1.63 with similar number of gains (1.18+/-1.17) and losses (1.00+/-1.34). The most frequent DNA copy number changes observed were losses of 9/9p (83%), followed by loss of 13q and gain of 7 (67%). Similar patterns of chromosome imbalances were observed in both blastic natural killer and cutaneous natural killer-like T cell lymphomas. Loss of the RB1 gene at 13q14.2 was detected in one blastic natural killer cell lymphoma with 13q loss using a gene dosage assay, and in one cutaneous natural killer-like T cell lymphoma without 13q loss using fluorescent in situ hybridization. Genomic microarray analysis identified oncogene copy number gains of PAK1 and JUNB in three of four cases studied, and gains of RAF1, CTSB, FGFR1, and BCR in two cases. Real-time polymerase chain reaction detected amplification of CTSB and RAF1 in four of five cases analyzed, JUNB and MYCN in three cases, and REL and YES1 in two cases, respectively. In conjunction with this study, an extensive literature search for the published G-banded karyotypes of four subsets of natural killer cell lymphomas was conducted, which showed a nonrandom pattern of multiple chromosome aberrations. These results reveal consistent genetic alterations in cutaneous natural killer cell lymphomas, and provide a basis for further investigation of molecular pathogenesis in this malignancy.

Amplification of the ABL gene in T-cell acute lymphoblastic leukemia

“…This technique has previously been shown to provide accurate analysis of gene copy number alteration in human tumors. 14,15 The value of 2.63 (Po0.001) for the ABL gene was significantly higher than copy number gains for other genes represented in this array. Thus, these data confirm that the high number of FISH signals observed represents amplification of the ABL gene.…”

Gene-expression profiling and array-based CGH classify CD4+CD56+ hematodermic neoplasm and cutaneous myelomonocytic leukemia as distinct disease entities

“…Using low-resolution comparative genomic hybridization (CGH), recurrent chromosomal abnormalities have been detected in 70% of cases, while fluorescent in situ hybridization studies demonstrated translocations involving chromosome 5q and 6q. 3,[7][8][9] Similar studies on c-AML are completely lacking.…”

Common and Contrasting Genomic Profiles among the Major Human Lung Cancer Subtypes

“…5A). As QPCR analysis clearly positioned the FGFR1 gene outside of the telomeric boundary of this MCR, and previous studies have implicated FGFR1 as the prime target of 8p amplicon in other cancer types (Simon et al 2001;Edwards et al 2003;Mao et al 2003), interphase FISH was used to verify the amplicon boundaries in several informative samples. Consistent with QPCR data, FISH with a BAC outside of the MCR and including FGFR1 on PT3 revealed only two copies (Fig.…”

“…Although novel for NSCLC, the amplicon on chromosome 8p has been observed in several other cancer types, including breast, prostate, bladder carcinomas, and T-cell lymphomas (Dib et al 1995;Simon et al 2001;Edwards et al 2003;Mao et al 2003;Ray et al 2004). Although FGFR1 resides within this larger CNA and has been considered the prime candidate target of this amplification, detailed QPCR and FISH mapping performed in this study defined both boundaries and narrowed the minimal common region that excludes the FGFR1 gene.…”