PMID- 15592718
OWN - NLM
STAT- MEDLINE
DCOM- 20050203
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 54
IP  - 2
DP  - 2005 Feb
TI  - High frequency of homozygosity of the HLA region in melanoma cell lines reveals a 
      pattern compatible with extensive loss of heterozygosity.
PG  - 141-8
AB  - Malignant transformation of cells is frequently associated with abnormalities in 
      human leukocyte antigen (HLA) expression. MHC class I loss or down-regulation in 
      cancer cells is a major immune escape route used by a large variety of human 
      tumours to evade antitumour immune responses mediated by cytotoxic T lymphocytes. 
      The goal of our study was to explore HLA genotyping and phenotyping in a variety 
      of melanoma tumour cell lines. A total of 91 melanoma cell lines were 
      characterised for HLA class I and II genotype. In addition, 61 out of the 91 cell 
      lines were also analysed for HLA class I and II cell surface molecule expression 
      by flow cytometry. Unexpectedly, we found that 19.7% of the melanoma cell lines 
      were homozygous for HLA class I genotypes, sometimes associated with HLA class II 
      homozygosity (8.79%) and sometimes not (10.98%). The frequency of homozygosity 
      was significantly higher compared with the control groups (1.6%). To identify the 
      reasons underlying the high frequency of HLA homozygosity we searched for genomic 
      deletions using eight pairs of highly polymorphic microsatellite markers covering 
      the entire extended HLA complex on the short arm of chromosome 6. Our results 
      were compatible with hemizygous deletions and suggest that loss of heterozygosity 
      on chromosome arm 6p is a common feature in melanoma cell lines. In fact, 
      although autologous normal DNA from the patients was not available and could not 
      be tested, the retention in some cases of heterozygosity for a number of 
      microsatellite markers would indicate a hemizygous deletion. In the rest of the 
      cases, markers at 6p and 6q showed a single allele pattern indicating the 
      probable loss of part or the whole of chromosome 6. These results led us to 
      conclude that loss of heterozygosity in chromosome 6 is nonrandom and is possibly 
      an immunologically relevant event in human malignant melanoma. Other 
      well-established altered HLA class I phenotypes were also detected by flow 
      cytometry that correspond to HLA class I total loss and HLA-ABC and/or specific 
      HLA-B locus down-regulation.
FAU - Rodriguez, Teresa
AU  - Rodriguez T
AD  - Departamento de Analisis Clinicos, Hospital Universitario Virgen de las Nieves, 
      Universidad de Granada, Avd. Fuerzas Armadas 2, 18014 Granada, Spain.
FAU - Mendez, Rosa
AU  - Mendez R
FAU - Roberts, Chrissy H
AU  - Roberts CH
FAU - Ruiz-Cabello, Francisco
AU  - Ruiz-Cabello F
FAU - Dodi, I Anthony
AU  - Dodi IA
FAU - Lopez Nevot, Miguel Angel
AU  - Lopez Nevot MA
FAU - Paco, Laura
AU  - Paco L
FAU - Maleno, Isabel
AU  - Maleno I
FAU - Marsh, Steven G E
AU  - Marsh SG
FAU - Pawelec, Graham
AU  - Pawelec G
FAU - Garrido, Federico
AU  - Garrido F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041001
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
SB  - IM
MH  - Chromosomes, Human, Pair 6/*genetics
MH  - Down-Regulation
MH  - Flow Cytometry
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, MHC Class I/*genetics
MH  - Genes, MHC Class II/*genetics
MH  - Genotype
MH  - Homozygote
MH  - Humans
MH  - *Loss of Heterozygosity
MH  - Melanoma/*genetics/immunology
MH  - Microsatellite Repeats
MH  - Phenotype
MH  - Skin Neoplasms/genetics/immunology
MH  - Tumor Cells, Cultured
PMC - PMC11032966
EDAT- 2004/12/14 09:00
MHDA- 2005/02/04 09:00
PMCR- 2004/10/01
CRDT- 2004/12/14 09:00
PHST- 2004/01/09 00:00 [received]
PHST- 2004/04/17 00:00 [accepted]
PHST- 2004/12/14 09:00 [pubmed]
PHST- 2005/02/04 09:00 [medline]
PHST- 2004/12/14 09:00 [entrez]
PHST- 2004/10/01 00:00 [pmc-release]
AID - 561 [pii]
AID - 10.1007/s00262-004-0561-5 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2005 Feb;54(2):141-8. doi: 10.1007/s00262-004-0561-5. 
      Epub 2004 Oct 1.