Table of Contents
1
UI - 11929831
AU - Selzer E; Wacheck V; Lucas T; Heere-Ress E; Wu M; Weilbaecher KN;
TI -
Schlegel W; Valent P; Wrba F; Pehamberger H; Fisher D; Jansen B
The melanocyte-specific isoform of the microphthalmia transcription
factor affects the phenotype of human melanoma.
SO - Cancer Res 2002 Apr 1;62(7):2098-103
AD - Department of Radiotherapy and Radiobiology, University Hospital Vienna,
1090 Vienna, Austria. Edgar.Selzer@AKH-Wien.ac.at
The microphthalmia transcription factor MITF plays a pivotal role in the
development and differentiation of melanocytes. The purpose of this work
was to investigate the expression and function of the
melanocyte-specific isoform MITF-M in human melanoma. We found that
MITF-M is repressed in 8 of 14 established melanoma cell lines tested.
Transfection of MITF-M into a melanoma cell line (518A2) lacking the
M-isoform and into a permanent cell line established from normal
melanocytes (NMel-II) resulted in slower tumor growth in a severe
combined immunodeficient-mouse xenotransplantation model. The growth
difference between vector control-transfected tumors derived from the
NMel-II cell line (mean tumor weight +/- SD, 3.2 g +/- 1.13) and MITF-M
(+) transfectants (mean tumor weight +/- SD, 1.1 g +/- 0.49) was
significant (P = 0.018). The mean tumor weight of control-transfected
518A2 tumors was 0.99 g +/- 0.22 and of MITF-M (+) transfectants, 0.69 g
+/- 0.32. The difference in growth between 518A2 controls and the MITF-M
(+) transfectants was clear, however it did not reach statistical
significance (P = 0.08). In addition to the growth-inhibitory effects,
MITF-M expression led to a change in the histopathological appearance of
tumors from epitheloid toward a spindle-cell type in vivo. These results
indicate a role for the MITF-M isoform in the in vivo growth control and
the phenotype of human melanoma. In conclusion, MITF-M may qualify as a
marker capable of identifying subgroups of melanoma patients with
different tumor biology and prognosis.
2
UI - 11920614
AU - de Wit NJ; Weidle UH; Ruiter DJ; van Muijen GN
TI -
Expression profiling of MMA-1a and splice variant MMA-1b: new
cancer/testis antigens identified in human melanoma.
SO - Int J Cancer 2002 Apr 1;98(4):547-53
AD - Department of Pathology, University Medical Centre St. Radboud,
Nijmegen, The Netherlands. n.dewit@pathol.azn.nl
Using high-density oligonucleotide array analysis, we have recently
compared the gene expression profiles of 2 human melanoma cell lines
with marked difference in metastatic behavior after subcutaneous
inoculation into nude mice (de Wit et al., Melanoma Res, in press). We
identified an expressed sequence tag (EST), which we called malignant
melanoma-associated 1 (MMA-1a), showing evident differential expression
between the 2 cell lines. The MMA-1a gene is localized on chromosome
21q22.2 and its mRNA exists of 4 exons. Homology search displayed a
splice variant of MMA-1a that lacks exon 3 and that was called MMA-1b.
Expression profiles of MMA-1a and MMA-1b are determined by reverse
transciptase polymerase chain reaction (RT-PCR) analysis. Among 30
different normal tissue samples, expression of MMA-1a and MMA-1b was
exclusively found in the testis after a first PCR of 30 cycles. Even
more sensitive screening achieved by performing multiple semi-nested
RT-PCR showed no or very low expression in the other normal tissues
tested. During melanocytic tumor progression, MMA-1a and/or MMA-1b
exhibited an emergence of expression in primary melanoma (20%) and
melanoma metastasis samples (30%) after only 1 round of PCR. Expression
of MMA-1a and/or MMA-1b was also identified in other tumor cell lines
and fresh tumor samples of variable origin, e.g., lung, liver, bladder
and soft tissues (sarcomas). We conclude that MMA-1a and MMA-1b are new
members of the family of cancer/testis antigens. Copyright 2002
Wiley-Liss, Inc.
3
UI - 11957144
AU - Maitra A; Gazdar AF; Moore TO; Moore AY
TI -
Loss of heterozygosity analysis of cutaneous melanoma and benign
melanocytic nevi: laser capture microdissection demonstrates clonal
genetic changes in acquired nevocellular nevi.
SO - Hum Pathol 2002 Feb;33(2):191-7
AD - Department of Pathology, the Hamon Center for Therapeutic Oncology
Research, University of Texas Southwestern Medical Center, Dallas, TX,
USA.
The molecular pathology of the common nevocellular nevus (NCN) and its
relationship to the genetic model of malignant melanoma (MM) progression
has not been fully characterized. We used laser capture microdissection
of archival formalin-fixed material to study 34 melanocytic lesions (19
MM and 15 NCN). Twelve of the 15 NCN were acquired, 3 of which were
congenital; none had dysplastic features. Ten polymorphic markers on
five chromosomal regions (1p36, 6q22-23.3, 8p22-24, 10q23, and 11q23)
were selected for loss of heterozygosity (LOH) analysis, based on
previous studies demonstrating involvement in MM pathogenesis and
progression. Loss of heterozygosity at any allelic locus was observed in
18 of 19 (95%) MM and in 9 of 15 (60%) NCN. Of the three congenital nevi
analyzed, none showed LOH at any informative locus. The frequency of
allelic loss was highest in the MM at 6q22-23.3 (64%), followed by 10q23
(62%), 8p22-24 (43%), 11q23 (43%), and 1p36 (13%). In the 15 NCN, the
most frequent allelic losses were detected at 6q22-23.3 (29%), 1p36
(27%), and 10q23 (25%), with lower frequencies of LOH at 11q23 (10%) and
8p22-24 (7%). LOH at a single polymorphic marker, D6S1038, was detected
in 70% of the MM and in 36% of the NCN, suggesting the presence of
putative tumor-suppressor genes (TSGs) critical in melanocytic neoplasia
at 6q22-23.3. The presence of clonal genetic alterations in acquired NCN
justifies their classification as a benign neoplasm. The pattern of LOH
in NCN is not random; rather, the relative frequencies of LOH at the
chromosomal regions examined are consistent with a multistep model of MM
progression that begins with NCN. Molecular analysis of NCN reiterates
established epidemiologic and morphologic notions that NCN are precursor
lesions for MM. Copyright 2002, Elsevier Science (USA). All rights
reserved.
4
UI - 11965544
AU - Tommasi S; Dammann R; Jin SG; Zhang Xf XF; Avruch J; Pfeifer GP
TI -
RASSF3 and NORE1: identification and cloning of two human homologues of
the putative tumor suppressor gene RASSF1.
SO - Oncogene 2002 Apr 18;21(17):2713-20
AD - Biology Department, Beckman Research Institute of the City of Hope,
Duarte, California, CA 91010, USA. stommasi@coh.org
RASSF1A, one of the two major isoforms of the putative tumor suppressor
gene RASSF1, located at 3p21.3, is inactivated in a variety of human
cancers including lung, breast, bladder and renal cell carcinomas. We
have isolated and cloned two human homologues of this gene, RASSF3 and
NORE1, located at 12q14.1 and 1q32.1, respectively. Both RASSF3 and
NORE1 share almost 60% homology, at the amino acid level, with RASSF1.
The RASSF3 gene contains five exons and encodes a 247 amino acid protein
(MW of 28.6 kDa) with a highly conserved Ras association (RalGDS/AF-6)
(RA) domain at the C-terminus. RASSF3 is ubiquitously expressed in all
normal tissues and cancer cell lines analysed. NORE1, which is
homologous to the previously described mouse Nore1 gene, exists in at
least two spliced isoforms, A and B. Transcript A encodes a protein of
418 amino acids (MW or 47 kDa) while transcript B contains an ORF of 265
aa (MW of 30.5 kDa). Both share a RA domain, encoded by exons 3 through
6. NORE1A and NORE1B are expressed in most of the normal tissues
analysed but they appear to be down-regulated in several cancer cell
lines. However, contrary to RASSF1A, gene silencing by methylation of
the CpG islands at which the two NORE1 transcripts initiate is not a
common event in human primary tumors. RASSF3 and NORE1B are very
similar, at the N-terminus, to the splice variant C of RASSF1 (RASSF1C),
which does not seem to be involved in tumorigenesis. NORE1A is most
closely related to RASSF1A, for sequence homology and genomic
organization. However, aberrations in tumors have so far not been found.
The presence of a Ras association domain common to NORE1, RASSF1, and
RASSF3 suggests their possible involvement in Ras-like signaling
pathways.
5
UI - 11809531
AU - Okada Y; Okada N; Nakagawa S; Mizuguchi H; Kanehira M; Nishino N;
TI -
Takahashi K; Mizuno N; Hayakawa T; Mayumi T
Fiber-mutant technique can augment gene transduction efficacy and
anti-tumor effects against established murine melanoma by cytokine-gene
therapy using adenovirus vectors.
SO - Cancer Lett 2002 Mar 8;177(1):57-63
AD - Department of Pharmaceutics, School of Pharmaceutical Sciences, Mukogawa
Women's University, 11-68 Kyuban-cho, Koshien, Nishinomiya, Hyogo
663-8179, Japan.
Melanoma cells are relatively resistant to adenovirus vector
(Ad)-mediated gene transfer due to the low expression of
Coxsackie-adenovirus receptor (CAR), which acts as a primitive
Ad-receptor. Therefore, extremely high doses of Ad are required for
effective gene therapy against melanoma. In the present study, we
investigated whether fiber-mutant Ad containing the Arg-Gly-Asp (RGD)
sequence in the fiber knob could promote gene delivery and anti-tumor
effects in the murine B16 BL6 tumor model. B16 BL6 cells (in vitro) and
tumors (in vivo) infected with RGD fiber-mutant Ad containing a tumor
necrosis factor alpha gene (Ad-RGD-TNFalpha) produced more TNFalpha than
those infected with conventional Ad-TNFalpha. In addition,
Ad-RGD-TNFalpha required about one-tenth the dosage of Ad-TNFalpha for
induction of equal therapeutic effects upon intratumoral injection into
established B16 BL6 tumors. Furthermore, the combination of both
TNFalpha- and interleukin 12-expressing RGD fiber-mutant Ads exhibited
more effective tumor regression than the Ad expressing each alone. These
results suggested that the fiber-mutant for altering Ad-tropism is a
very potent technology for advancing gene therapy for melanoma.
6
UI - 11950921
AU - Demunter A; Libbrecht L; Degreef H; De Wolf-Peeters C; van den Oord JJ
TI -
Loss of membranous expression of beta-catenin is associated with tumor
progression in cutaneous melanoma and rarely caused by exon 3 mutations.
SO - Mod Pathol 2002 Apr;15(4):454-61
AD - Department of Pathology, Laboratory of Morphology and Molecular
Pathology, University Hospitals, Katholieke Universiteit Leuven,
Belgium. anouk.demunter@uz.kuleuven.ac.be
beta-Catenin plays a fundamental role in the regulation of the
E-cadherin-catenin cell adhesion complex. It also plays a role in the
Wnt signaling pathway by activating T-cell factor- and lymphoid enhancer
factor-regulated gene transcription. The level of beta-catenin in cells
is tightly controlled in a multiprotein complex, and mutations in the
glycogen synthase kinase 3beta (GSK-3beta) phosphorylation sites of the
beta-catenin gene (CTNNB1) result in nuclear and/or cytoplasmic
accumulation of beta-catenin and constitutive transactivation of T-cell
factor and lymphoid enhancer factor target genes, a mechanism occurring
in many cancers. Melanoma cell lines may harbor beta-catenin mutations;
in vivo, however, cellular accumulation of beta-catenin is rarely caused
by CTNNB1 mutations. In our study, 43 primary cutaneous melanoma and 30
metastases were screened for CTNNB1 exon 3 mutations by using a
denaturing gradient gel electrophoresis technique and sequencing.
beta-Catenin mutations were found in 2 primary melanomas and 1
metastatic melanoma and were not correlated with nuclear accumulation of
beta-catenin in these cases. Cellular expression of beta-catenin was
evaluated by immunohistochemistry and by reverse polymerase chain
reaction (RT-PCR) in 80 and 70 cases, respectively. Immunohistochemistry
revealed a significant loss of membranous beta-catenin staining between
the primary and metastatic melanomas as well as between radial and
vertical growth phase. RT-PCR showed a significant inverse correlation
between the amount of RNA and the proportion of cells with membranous
expression of beta-catenin (P =.0015); no correlation existed between
the amount of RNA and the number of cells with nuclear or cytoplasmic
expression of beta-catenin. In conclusion, nuclear expression of
beta-catenin is seen in cutaneous melanoma but, in contrast to the case
of many other cancers, does not correlate with tumor stage or mutation
status. A combination of immunohistochemistry and RT-PCR showed that
down-regulation of membranous beta-catenin was associated with an
increased amount of beta-catenin RNA in primary or metastatic melanoma.
Our results suggest that posttranslational events, rather than CTNNB1
mutations, are responsible for the altered distribution of beta-catenin
in cutaneous melanoma.
7
UI - 11996799
AU - Guan XY; Zhang HE; Zhou H; Sham JS; Fung JM; Trent JM
TI -
Characterization of a complex chromosome rearrangement involving 6q in a
melanoma cell line by chromosome microdissection.
SO - Cancer Genet Cytogenet 2002 Apr 1;134(1):65-70
AD - Department of Clinical Oncology, The University of Hong Kong, Room 122,
Professorial Block, Pokfulam Road, Hong Kong, China. xyguan@hkucc.hku.hk
Deletion of 6q is one of the most frequent chromosomal alterations in
human malignant melanoma. Recently, we used chromosome painting probes
of 6p and 6q to study 21 melanoma cell lines. A reciprocal translocation
between chromosomes 6q and 17p was detected in one cell line (UACC-930).
Upon further characterization of the translocation marker using the
micro fluorescence in situ hybridization (FISH) technique, a complex
rearrangement including an inversion of 6q and a translocation between
the inverted 6q and 17p, [der(6)inv(6)(q16q27)t(6;17)(q26;p13)], was
detected. A yeast artificial chromosome (YAC) clone spanning the
breakpoint at 6q16 was isolated by the FISH screen. Loss of one or more
copies of the YAC clone was also detected in 10 of 12 melanoma cell
lines. This result implies that the YAC clone may contain a putative
tumor suppressor gene related to the pathogenesis of malignant melanoma.
Further characterizations of the breakpoint at 6q16 and molecular
cloning breakpoints at 6q27 and 17p13 are in progress.
8
UI - 11971032
AU - Linard B; Bezieau S; Benlalam H; Labarriere N; Guilloux Y; Diez E;
TI -
Jotereau F
A ras-mutated peptide targeted by CTL infiltrating a human melanoma
lesion.
SO - J Immunol 2002 May 1;168(9):4802-8
AD - Institut de Biologie, Institut National de la Sante et de la Recherche
Medicale, Unite 463, and Faculte des Sciences et Techniques de Nantes,
Nantes, France. blinard@nantes.inserm.fr
Ags derived from commonly mutated oncogenic proteins seem ideally suited
as targets for tumor immunotherapy. Nonetheless, only a few mutated
epitopes efficiently presented by human tumors have thus far been
identified. We describe here an approach to identify such epitopes. This
approach involves: 1) identifying tumors expressing a ras mutation and
isolating the tumor-infiltrating lymphocytes (TIL); 2) transfecting COS
cells to induce expression of unknown mutated peptides in the context of
a patient's HLA class I molecules; and 3) screening epitope recognition
by using TIL from the tumors expressing a ras mutation. By using this
approach, there appeared to be a N-ras mutation (a glutamine-to-arginine
exchange at residue 61 (Q61R)), detected in a melanoma lesion, which was
recognized specifically by the autologous TIL in the HLA-A*0101 context.
The ras peptide 55-64(Q61R) was the epitope of these TIL and was
regularly presented by Q61R-mutated HLA-A*0101(+) melanoma cell lines.
This peptide and its wild-type homolog (55-64(wt)) bound to HLA-A*0101
with similar affinities. However, only the mutated peptide could induce
specific CTL expansion from PBL. All the CTL clones specific to the
mutated peptide, failed to recognize the wild-type sequence on both COS
and melanoma cells. These data thus show that oncogenic protein
mutations can create shared tumor-specific CTL epitopes, efficiently
presented by tumor cells, and that screening for oncogene-transfected
COS cell recognition by TIL (from tumors containing mutations) is a
powerful approach for the identification of these epitopes.
9
UI - 11863416
AU - Martin F; Chowdhury S; Neil S; Phillipps N; Collins MK
TI -
Envelope-targeted retrovirus vectors transduce melanoma xenografts but
not spleen or liver.
SO - Mol Ther 2002 Mar;5(3):269-74
AD - Department of Immunology and Molecular Pathology, Windeyer Institute of
Medical Science, University College London, 46 Cleveland Street, London
W1P 6DB, UK. f.martin-molina@ucl.ac.uk
Many cancer gene therapy applications would benefit from the development
of targeted vectors that could deliver genes in vivo. We have previously
achieved efficient in vitro targeting of retrovirus vectors to melanoma
cells by fusion of a single chain antibody recognizing the
high-molecular-weight melanoma-associated antigen (HMWMAA), followed by
a blocking peptide and a matrix metalloprotease cleavage site, to the
amino terminus of the murine leukemia virus amphotropic strain envelope.
Here we report that up to 3% of cells within an HMWMAA-positive tumor
xenograft were infected following a single injection of targeted vector
into the tumor and up to 10% of tumor cells became infected when they
were co-injected with viral producer cells. No infected cells were
detected after delivery of targeted vectors to HMWMAA-negative tumor
xenografts. Intraperitoneal injection of amphotropic vectors or producer
cells resulted in transduction in spleen and liver, which was not
detected when targeted vectors or producer cells were used. Our results
demonstrate the feasibility of using targeted retroviral vectors for in
vivo gene delivery to tumors and highlight the safety benefits of
targeted vectors that do not infect other host tissues.
10
UI - 11882905
AU - Ladanyi A; Gallai M; Paku S; Nagy JO; Dudas J; Timar J; Kovalszky I
TI -
Expression of a decorin-like moleculein human melanoma.
SO - Pathol Oncol Res 2001;7(4):260-6
AD - National Institute of Oncology, Department of Tumor Progression Rath Gy.
u.7-9., Budapest, H-1122, Hungary.
Decorin, a member of the family of small leucin-rich proteoglycans, has
originally been described as a secreted proteoglycan component of the
connective tissues, and has been implicated in the negative regulation
of cell proliferation directly or via interactions with TGF-beta. It was
reported to be generally absent from tumor cells. Here we show that
human melanoma cell lines express a decorin-like molecule. We detected
decorin mRNA by RT-PCR in 7 out 7 human melanoma lines characterized by
various metastatic potential. Using polyclonal antiserum against the
core protein of decorin, the typical 80-120 kD glycanated form as well
as a high molecular weight aberrant version (200-210 kD) of decorin were
demonstrated by Western blot technique in the culture supernatants as
well as in lysates of human melanoma cells. Finally, decorin epitope was
also demonstrated immunohistochemically in human melanoma xenografts, as
well as in tumor cells of surgically resected melanomas but not in
melanocytes of nevi.The expression of this aberrant decorin did not
inhibit the in vitroor in vivogrowth of human melanoma cells, and it was
independent of their metastatic potential. Human melanoma cell lines
expressing aberrant decorin retained sensitivity to the
antiproliferative and gelatinase-stimulatory effects of exogenous
TGF-beta.
11
UI - 11959101
AU - Raisova M; Goltz G; Bektas M; Bielawska A; Riebeling C; Hossini AM;
TI -
Eberle J; Hannun YA; Orfanos CE; Geilen CC
Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors
in malignant melanoma and HaCaT keratinocytes.
SO - FEBS Lett 2002 Apr 10;516(1-3):47-52
AD - Department of Dermatology, University Medical Center Benjamin Franklin,
The Free University of Berlin, 14195, Berlin, Germany.
We examined the biological effects of the ceramide analogues
(1S,2R)-2-N-myristoylamino-1-phenyl-1-propanol (D-e-MAPP) and
(1R,2R)-2-N-myristoylamino-1-(4-nitrophenyl)-1,3-propandiol (D-NMAPPD)
on human HaCaT keratinocytes and human melanoma cells. We could
demonstrate that D-e-MAPP and D-NMAPPD are able to suppress acid
ceramidase activity. The elevation of the endogenous level of ceramide
is followed by induction of apoptosis and suppression of proliferation
in HaCaT keratinocytes. Moreover, we recently identified a group of
human melanoma cell populations which are heterogeneously susceptible to
C2-ceramide-mediated apoptosis. Studies with these melanoma cells
revealed correlation between ceramide-mediated apoptosis and
D-NMAPPD-induced apoptosis, confirming the effect of this inhibitor on
ceramide signaling in human melanoma cells. These findings suggest
ceramidase inhibitors as a potential new therapeutical class of
antiproliferative and cytostatic drugs.
12
UI - 11839674
AU - Naus NC; Verhoeven AC; van Drunen E; Slater R; Mooy CM; Paridaens DA;
TI -
Luyten GP; de Klein A
Detection of genetic prognostic markers in uveal melanoma biopsies using
fluorescence in situ hybridization.
SO - Clin Cancer Res 2002 Feb;8(2):534-9
AD - Department of Ophthalmology, Erasmus University Rotterdam, 3000 DR
Rotterdam, the Netherlands.
PURPOSE: In uveal melanoma, specific chromosomal abnormalities are known
to correlate with the risk of metastases; changes in chromosomes 3 and
8q correlate strongly with a decreased survival of the patient, whereas
chromosome 6 abnormalities are associated with a better prognosis.
Usually, karyotyping and fluorescence in situ hybridization (FISH)
analysis are used to detect these abnormalities in resected tumor
tissues. However, the evaluation of these chromosomal changes is
compromised in patients treated with eye-retaining treatment protocols
because of the lack of tumor material. The purpose of this study was to
validate the use of FISH for the analysis of genetic prognostic markers.
EXPERIMENTAL DESIGN: We analyzed 40 uveal melanoma fine needle
aspiration biopsies (FNABs) and the corresponding main tumor with FISH.
RESULTS: All biopsies were found to contain tumor cells, and FISH
analyses of the samples were successful in all cases. Statistical
analysis showed very good agreement between the FISH results from the
biopsies and those from the main tumor. In only 2 of 249 hybridizations
did we find a small variation that could have led to a
misclassification. CONCLUSIONS: Our results indicate that the
application of FISH to FNABs is a reliable method for assaying genetic
prognostic parameters such as chromosome 3 loss and/or chromosome 8q
gain. Implementation of this method in a diagnostic setting means that
we are able to identify patients at risk of developing metastatic
disease, not only in enucleated patients but also in cases treated with
conservative treatment modalities such as radiotherapy.
13
UI - 11896445
AU - Grangeon C; Cormary C; Douin-Echinard V; Favre G; Couderc B;
TI -
Tilkin-Mariame AF
In vivo induction of antitumor immunity and protection against tumor
growth by injection of CD154-expressing tumor cells.
SO - Cancer Gene Ther 2002 Mar;9(3):282-8
AD - Laboratoire d'Oncologie Cellulaire et Moleculaire, EA/UPRES 2048,
Institut Claudius Regaud 20-24, rue du Pont Saint-Pierre, Toulouse Cedex
31052, France.
As they should enhance tumor-specific antigen presentation by dendritic
cells, tumor cell lines genetically modified to express CD154 molecules
have been used in an attempt to induce protective antitumor immunity.
Two murine models were used: the major histocompatibility complex (MHC)
class I negative melanoma B16F10 and the MHC class I positive mammary
adenocarcinoma TS/A. CD154 or mock-transfected B16F10 or TS/A cells were
injected subcutaneously into H-2-compatible B6D2 mice. CD154 expression
by tumor cells induced a complete rejection (in the TS/A model) or a
striking reduction (in the B16F10 model) of modified tumors growth, but
also a significant protection against the growth of mock tumor cells
injected simultaneously, either mixed with the CD154-expressing tumor
cells, or in the other flank of mice. Thirty days after CD154-expressing
tumor rejection, splenic lymphocytes from surviving tumor-free mice were
able to inhibit tumor proliferation in vitro and significant amounts of
IFN-gamma were detected in the sera of these mice. Growth kinetics of
mock and CD154-expressing tumors in immunocompetent versus nude mice
suggest that T lymphocytes and natural killer cells responses are
implicated in this antitumor immunity. The injection of CD154-expressing
tumor cell induced an antitumor protective response, both locally and
distant from the injection site. The effect was most pronounced in MHC
class I expressing TS/A tumor model.
14
UI - 10900104
AU - Singh AD; Shields CL; Shields JA; Sato T
TI -
Uveal melanoma in young patients.
SO - Arch Ophthalmol 2000 Jul;118(7):918-23
AD - Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA
19107, USA. arunsingh@eyetumors.com
OBJECTIVE: To study the clinical profile of young patients with uveal
melanoma. DESIGN: Retrospective case-control series. SETTING: Tertiary
referral center. PATIENTS: Data on 63 patients aged 20 years or younger
with uveal melanoma were reviewed for clinical profile and association
with oculo(dermal) melanocytosis, familial uveal melanoma, dysplastic
nevus syndrome, cutaneous melanoma, and other second malignant
neoplasms. RESULTS: Of 8000 patients with uveal melanoma, 63 (0.8%) were
found in patients who were 20 years of age or younger. The median age at
diagnosis was 16 years, and the youngest patient was 3 years old.
Sixty-two patients (98%) were white, and uveal melanoma was unilateral
in all cases. Seven patients (11%) had oculo(dermal) melanocytosis. Two
patients (3%) had dysplastic nevi syndrome, and personal history of
cutaneous melanoma was observed in 1 patient (2%). No other second
cancers were present in any patient. The 5- and 15-year posttreatment
survival estimates were 0.95 (95% confidence interval, 0.87-1.00) and
0.77 (95% confidence interval, 0.52-1.00), respectively. CONCLUSIONS:
Uveal melanoma is rare in children or teenagers. It occurs in a
heterogeneous group displaying various associations, especially with
oculo(dermal) melanocytosis. Oculo(dermal) melanocytosis is 9 times (95%
confidence interval, 3.6-22.8) more common in young patients with uveal
melanoma than in the general population with uveal melanoma. Young
patients with uveal melanoma have short-term (5-year) survival better
than that of adults, but the long-term (15-year) survival is similar to
that of adults. Arch Ophthalmol. 2000;118:918-923
15
UI - 11836553
AU - Wai DH; Schaefer KL; Schramm A; Korsching E; Van Valen F; Ozaki T;
TI -
Boecker W; Schweigerer L; Dockhorn-Dworniczak B; Poremba C
Expression analysis of pediatric solid tumor cell lines using
oligonucleotide microarrays.
SO - Int J Oncol 2002 Mar;20(3):441-51
AD - Gerhard-Domagk-Institute of Pathology, University of Muenster, D-48149
Muenster, Germany.
We identified patterns of differentially-expressed genes in cell lines
derived from several pediatric solid tumors. Affymetrix Human Cancer
G110 Arrays, carrying 1,700 cancer-associated genes, were applied to a
panel of 11 cell lines originating from Ewing tumors (ETs),
neuroblastomas, and malignant melanoma of soft parts. Hierarchical
clustering clearly differentiated these 3 entities and revealed groups
of 75, 102, and 36 gene probe-sets exhibiting tumor-type specific
up-regulation in these cell lines, respectively. Whereas ET lines
demonstrated increased expression of microtubule-associated protein tau
(MAPT), protein phosphatase 1 regulatory subunit 1A (PPP1R1A), NIMA
(never in mitosis gene a)-related kinase 2 (NEK2), and cyclin D1
(CCND1), neuroblastoma samples exhibited high expression of
wingless-type mouse mammary tumor virus integration site family member
11 (WNT11), Drosophila frizzled homolog 2 (FZD2), and adenomatous
polyposis coli (APC) which are involved in regulating free beta-catenin
levels. These genes likely maintain tumor-specific characteristics and
participate in key downstream regulatory mechanisms. We also correlated
the expression levels of up-regulated genes in ETs with their
chromosomal localization and compared these data to the comparative
genomic hybridization profiles of the cell lines. We demonstrate that
gains of genetic material contribute essentially to differential gene
expression.
16
UI - 11836561
AU - Eleveld-Trancikova D; Kudela P; Majerciak V; Regendova M; Zelnik V;
TI -
Pastorek J; Pastorekova S; Bizik J
Suppression subtractive hybridisation to isolate differentially
expressed genes involved in invasiveness of melanoma cell line cultured
under different conditions.
SO - Int J Oncol 2002 Mar;20(3):501-8
AD - Department of Tumor Cell Biology, Cancer Research Institute, Slovack
Academy of Sciences, 833 91 Bratislava, Slovakia. d.eleveld@ncmls.kun.nl
We have previously analysed the invasion capacity of different melanoma
cell lines in the three-dimensional dermal equivalent. The melanoma cell
line M4Beu acquired invasive behaviour upon changing its cultivation
conditions before the seeding on top of the collagen lattice from single
cell suspension to spheroid. Based on this phenomenon SSH was used to
search for the genes related to the invasive phenotype of melanoma
cells. From differentially expressed clones we focused on four:
fibronectin, RhoA, COXII, and H-ras-like protein. By RT-PCR the
expression of these genes were tested in different populations
(monolayer, spheroids on dermal equivalent) of melanoma cell line M4Beu
and three additional melanoma cell lines. The expression of fibronectin
was also examined by immunohistochemistry staining of co-culture
spheroids-dermal equivalent.
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