1: J Invest Dermatol. 2003 Sep;121(3):618-27. 

Genomic alterations in blastic natural killer/extranodal natural killer-like T
cell lymphoma with cutaneous involvement.

Mao X, Onadim Z, Price EA, Child F, Lillington DM, Russell-Jones R, Young BD,
Whittaker S.

Skin Tumour Unit, St John's Institute of Dermatology, 4th Floor, South Wing
Block 7, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
mxmayo@yahoo.co.uk

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.

PMID: 12925224 [PubMed - indexed for MEDLINE]


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2: Genes Chromosomes Cancer. 2003 Jun;37(2):176-85. 

Genetic alterations in primary cutaneous CD30+ anaplastic large cell lymphoma.

Mao X, Orchard G, Lillington DM, Russell-Jones R, Young BD, Whittaker S.

Skin Tumour Unit, St. John's Institute of Dermatology, St. Thomas' Hospital,
London, United Kingdom. mxmayo@yahoo.co.uk

Primary cutaneous CD30+ anaplastic large cell lymphoma (C-ALCL) represents a
distinct clinical subtype of CD30+ anaplastic large cell lymphomas. The etiology
and underlying molecular pathogenesis of C-ALCL remain unclear. This study aimed
to investigate genetic changes in C-ALCL. Comparative genomic hybridization
(CGH) analysis of 23 DNA samples from 15 C-ALCL cases identified chromosome
imbalances (CI) in 10 samples from eight cases (43%). The mean number of CI per
sample was 2.09 +/- 3.86, with gains (2.00 +/- 3.85) more common than losses
(0.09 +/- 0.29). The most frequent CI were gains of 1/1p and 5 (50%) and 6, 7,
8/8p, and 19 (38%). Microarray-based CGH analysis of six DNA samples from five
cases with CI revealed genomic imbalances (GI) in all of the cases studied. This
included oncogene copy number gains of FGFR1 (8p11) in three cases, and NRAS
(1p13.2), MYCN (2p24.1), RAF1 (3p25), CTSB (8p22), FES (15q26.1), and CBFA2
(21q22.3) in two cases. Real-time PCR analysis of nine DNA samples from eight
cases with CI and GI detected amplifications of CTSB and RAF1 in seven cases
(88%), REL (2p13p12) and JUNB (19p13.2) in six cases (75%), and MYCN and YES1
(18p11.3) in four cases (50%). Immunohistochemical staining of paraffin sections
from six cases demonstrated expression of JUNB protein in five cases and BCL2 in
three cases. These results reveal a consistent pattern of genetic alterations in
C-ALCL and provide the molecular basis for further investigation of this
disease. Copyright 2003 Wiley-Liss, Inc.

PMID: 12696066 [PubMed - indexed for MEDLINE]


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