PMID- 23784959
OWN - NLM
STAT- MEDLINE
DCOM- 20131204
LR  - 20210103
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 134
IP  - 1
DP  - 2014 Jan 1
TI  - Immune escape of cancer cells with beta2-microglobulin loss over the course of 
      metastatic melanoma.
PG  - 102-13
LID - 10.1002/ijc.28338 [doi]
AB  - Cancer cells escape T-cell-mediated destruction by losing human leukocyte antigen 
      (HLA) class I expression via various mechanisms, including loss of 
      beta2-microglobulin (beta2m). Our study illustrates the immune escape of HLA class 
      I-negative tumor cells and chronological sequence of appearance of tumor beta2m gene 
      mutation in successive lesions obtained from a patient with metastatic melanoma. 
      We observed a gradual decrease in HLA expression in consecutive lesions with few 
      HLA-negative nodules in the primary tumor and the emergence of a totally negative 
      lesion at later stages of the disease. We detected loss of beta2m in beta2m-negative 
      nests of the primary tumor caused by a combination of two alterations: (i) a 
      mutation (G to T substitution) in codon 67 in exon 2 of beta2m gene, producing a 
      stop codon and (ii) loss of the second gene copy by loss of heterozygosity (LOH) 
      in chromosome 15. The same beta2m mutation was found in a homogeneously beta2m-negative 
      metastasis 10 months later and in a cell line established from a biopsy of a 
      postvaccination lymph node. Microsatellite analysis revealed the presence of LOH 
      in chromosomes 6 and 15 in tumor samples, showing an accumulation of chromosomal 
      loss at specific short tandem repeats in successive metastases during disease 
      progression. HLA loss correlated with decreased tumor CD8+ T-cell infiltration. 
      Early incidence of beta2m defects can cause an immune selection and expansion of 
      highly aggressive melanoma clones with irreversible genetic defects causing total 
      loss of HLA class I expression and should be taken into consideration as a 
      therapeutic target in the development of cancer immunotherapy protocols.
CI  - (c) 2013 UICC.
FAU - del Campo, Ana B
AU  - del Campo AB
AD  - Department of Clinical Analysis and Immunology, University Hospital Virgen de las 
      Nieves, Granada, Spain; Department of Biochemistry, Molecular Biology III and 
      Immunology, University of Granada Medical School, Granada, Spain.
FAU - Kyte, Jon Amund
AU  - Kyte JA
FAU - Carretero, Javier
AU  - Carretero J
FAU - Zinchencko, Svitlana
AU  - Zinchencko S
FAU - Mendez, Rosa
AU  - Mendez R
FAU - Gonzalez-Aseguinolaza, Gloria
AU  - Gonzalez-Aseguinolaza G
FAU - Ruiz-Cabello, Francisco
AU  - Ruiz-Cabello F
FAU - Aamdal, Steinar
AU  - Aamdal S
FAU - Gaudernack, Gustav
AU  - Gaudernack G
FAU - Garrido, Federico
AU  - Garrido F
FAU - Aptsiauri, Natalia
AU  - Aptsiauri N
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130716
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (beta 2-Microglobulin)
SB  - IM
MH  - Aged
MH  - Cell Line, Tumor
MH  - Flow Cytometry
MH  - Histocompatibility Antigens Class I/*biosynthesis/genetics/immunology
MH  - Humans
MH  - Immunohistochemistry
MH  - Loss of Heterozygosity
MH  - Melanoma/*genetics/immunology/pathology
MH  - Mutation
MH  - Neoplasm Invasiveness/genetics/pathology
MH  - Neoplasm Metastasis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Escape/*genetics/immunology
MH  - beta 2-Microglobulin/*genetics/immunology
OTO - NOTNLM
OT  - beta2-microglobulin mutation
OT  - immune escape
OT  - metastatic melanoma
OT  - tumor HLA class I loss
EDAT- 2013/06/21 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/06/21 06:00
PHST- 2013/03/29 00:00 [received]
PHST- 2013/03/31 00:00 [accepted]
PHST- 2013/06/21 06:00 [entrez]
PHST- 2013/06/21 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - 10.1002/ijc.28338 [doi]
PST - ppublish
SO  - Int J Cancer. 2014 Jan 1;134(1):102-13. doi: 10.1002/ijc.28338. Epub 2013 Jul 16.