Evidence map›Paper›PMID 23018810›Full record

ArticlemAbs

Identification of a single base-pair mutation of TAA (Stop codon) → GAA (Glu) that causes light chain extension in a CHO cell derived IgG1.

Taylor Zhang, Yungfu Huang, Scott Chamberlain, Tony Romeo, Judith Zhu-Shimoni, Daniel Hewitt, Mary Zhu, Viswanatham Katta, Brad Mauger, Yung-Hsiang Kao

Open access · goldAbstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

10 citing papers in PubMed, 27 citations in OpenAlex.

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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

10 authors at 2 institutions in 1 country.

Taylor ZhangProtein Analytical Chemistry, Genentech, South San Francisco, CA, USA. yonghuaz@gene.com
Yungfu Huang
Scott Chamberlain
Tony Romeo
Judith Zhu-Shimoni
Daniel Hewitt
Mary Zhu
Viswanatham Katta
Brad Mauger
Yung-Hsiang Kao
GenentechGene Therapy Laboratory · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We describe here the identification of a stop codon TAA (Stop) → GAA (Glu) = Stop221E mutation on the light chain of a recombinant IgG1 antibody expressed in a Chinese hamster ovary (CHO) cell line. The extended light chain variants, which were caused by translation beyond the mutated stop codon to the next alternative in-frame stop codon, were observed by mass spectra analysis. The abnormal peptide peaks present in tryptic and chymotryptic LC-MS peptide mapping were confirmed by N-terminal sequencing as C-terminal light chain extension peptides. Furthermore, LC-MS/MS of Glu-C peptide mapping confirmed the stop221E mutation, which is consistent with a single base-pair mutation in TAA (stop codon) to GAA (Glu). The light chain variants were approximately 13.6% of wild type light chain as estimated by RP-HPLC analysis. DNA sequencing techniques determined a single base pair stop codon mutation, instead of a stop codon read-through, as the cause of this light chain extension. To our knowledge, the stop codon mutation has not been reported for IgGs expressed in CHO cells. These results demonstrate orthogonal techniques should be implemented to characterize recombinant proteins and select appropriate cell lines for production of therapeutic proteins because modifications could occur at unexpected locations.

Indexed as

AnimalsBase Pair MismatchCHO CellsCodon, TerminatorCricetinaeCricetulusDNA Mutational AnalysisGlutamineImmunoglobulin GImmunoglobulin Light ChainsMass SpectrometryMutationProtein IsoformsRNA Processing, Post-TranscriptionalCodon, TerminatorGlutamineImmunoglobulin GImmunoglobulin Light ChainsProtein IsoformsdetectionIgG1mutationsequence variantsstop codon

Identifiers

PMID23018810
PMCPMC3502236
OpenAlexW1988701639

What OpenQuestion holds

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Registered trials

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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.