Evidence map›Paper›PMID 10432284›Full record

ArticleThe Journal of experimental medicine1999

Selective histocompatibility leukocyte antigen (HLA)-A2 loss caused by aberrant pre-mRNA splicing in 624MEL28 melanoma cells.

Z Wang, F M Marincola, L Rivoltini, G Parmiani, S Ferrone

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 103 citations in OpenAlex.

  1. Review
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  3. Article
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  5. Review
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  7. Review
  8. Article
  9. Defective HLA class I antigen processing machinery in cancer.Cancer immunology, immunotherapy : CII · 2018
    Article
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  11. Review
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  19. Tumor immune escape mechanisms: impact of the neuroendocrine system.Cancer immunology, immunotherapy : CII · 2006
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Z WangDepartment of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
F M Marincola
L Rivoltini
G Parmiani
S Ferrone
Fondazione IRCCS Istituto Nazionale dei Tumori · ITRoswell Park Comprehensive Cancer Center · USNational Institutes of Health Clinical Center · US

Funding

HLA CLASS I PEPTIDE COMPLEX ADNORMALITIES IN MELANOMAR01CA067108 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FERRONE, SOLDANO · 1996 to 2004
$1.5M
NCI NIH HHS CA67108NCI NIH HHS R01 CA067108
6 · The paper itself

Abstract

Histocompatibility leukocyte antigen (HLA)-A2 is used as a restricting element to present several melanoma-associated antigen (MAA)-derived peptides to cytotoxic T lymphocytes (CTLs). HLA-A2 antigen is selectively lost in primary melanoma lesions and more frequently in metastases. Only scanty information is available about the molecular mechanisms underlying this abnormality, in spite of its potentially negative impact on the clinical course of the disease and on the outcome of T cell-based immunotherapy. Therefore, in this study we have shown that the selective HLA-A2 antigen loss in melanoma cells 624MEL28 is caused by a splicing defect of HLA-A2 pre-mRNA because of a base substitution at the 5' splice donor site of intron 2 of the HLA-A2 gene. As a result, HLA-A2 transcripts are spliced to two aberrant forms, one with exon 2 skipping and the other with intron 2 retention. The latter is not translated because of an early premature stop codon in the retained intron. In contrast, the transcript with exon 2 skipping is translated to a truncated HLA-A2 heavy chain without the alpha(1) domain. Such a polypeptide is synthesized in vitro but is not detectable in cells, probably because of the low steady state level of the corresponding mRNA and the low translation efficiency. These results indicate that a single mutational event in an HLA class I gene is sufficient for loss of the corresponding allele. This may account, at least in part, for the high frequency of selective HLA class I allele loss in melanoma cells. Our conclusion emphasizes the need to implement active specific immunotherapy with a combination of peptides presented by various HLA class I alleles. This strategy may counteract the ability of melanoma cells with selective HLA class I allele loss to escape from immune recognition.

Indexed as

Alternative SplicingAmino Acid SequenceBase SequenceDNA, ComplementaryDNA, NeoplasmDNA PrimersGene ExpressionGenes, MHC Class IHLA-A2 AntigenHumansImmunotherapyIntronsMelanomaMolecular Sequence DataMutationRNA, NeoplasmDNA, ComplementaryDNA, NeoplasmDNA PrimersHLA-A2 AntigenRNA, NeoplasmRNA Precursors

Identifiers

PMID10432284
PMCPMC2195569
OpenAlexW2125467688

What OpenQuestion holds

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LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.