Evidence map›Paper›PMID 22017758›Full record

ArticleJournal of experimental & clinical cancer research : CR2011

Detection of DNA mismatch repair proteins in fresh human blood lymphocytes--towards a novel method for hereditary non-polyposis colorectal cancer (Lynch syndrome) screening.

Samar Hassen, Bruce M Boman, Nawab Ali, Marcie Parker, Chandra Somerman, Zohra J Ali-Khan Catts, Akhtar A Ali, Jeremy Z Fields

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 34% 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

3 citing papers in PubMed, 4 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

8 authors at 2 institutions in 1 country.

Samar HassenCATX Inc., Gladwyne, PA 19035, USA.
Bruce M Boman
Nawab Ali
Marcie Parker
Chandra Somerman
Zohra J Ali-Khan Catts
Akhtar A Ali
Jeremy Z Fields
UCSF Helen Diller Family Comprehensive Cancer Center · USUniversity of Arkansas at Little Rock · US

Funding

Screening Pretest for HNPCCR44CA090122 · NCI · CA*TX, INC. · PI FIELDS, JEREMY Z · 2006 to 2007
$720k
NCI NIH HHS R44 CA 090122
6 · The paper itself

Abstract

backgroundA broad population-based assay to detect individuals with Lynch Syndrome (LS) before they develop cancer would save lives and healthcare dollars via cancer prevention. LS is caused by a germline mutation in a DNA mismatch repair (MMR) gene, especially protein truncation-causing mutations involving MSH2 or MLH1. We showed that immortalized lymphocytes from LS patients have reduced levels of full-length MLH1 or MSH2 proteins. Thus, it may be feasible to identify LS patients in a broad population-based assay by detecting reduced levels of MMR proteins in lymphocytes.

methodsAccordingly, we determined whether MSH2 and MLH1 proteins can also be detected in fresh lymphocytes. A quantitative western blot assay was developed using two commercially available monoclonal antibodies that we showed are specific for detecting full-length MLH1 or MSH2. To directly determine the ratio of the levels of these MMR proteins, we used both antibodies in a multiplex-type western blot.

resultsMLH1 and MSH2 levels were often not detectable in fresh lymphocytes, but were readily detectable if fresh lymphocytes were first stimulated with PHA. In fresh lymphocytes from normal controls, the MMR ratio was ~1.0. In fresh lymphocytes from patients (N > 50) at elevated risk for LS, there was a bimodal distribution of MMR ratios (range: 0.3-1.0).

conclusionsFinding that MMR protein levels can be measured in fresh lymphocytes, and given that cells with heterozygote MMR mutations have reduced levels of full-length MMR proteins, suggests that our immunoassay could be advanced to a quantitative test for screening populations at high risk for LS.

Indexed as

DNA Mismatch RepairAdaptor Proteins, Signal TransducingCell Line, TumorCells, CulturedColorectal Neoplasms, Hereditary NonpolyposisEarly Detection of CancerGerm-Line MutationHCT116 CellsHumansLymphocytesMutL Protein Homolog 1MutS Homolog 2 ProteinNuclear ProteinsAdaptor Proteins, Signal TransducingMLH1 protein, humanMSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinNuclear Proteins

Identifiers

PMID22017758
PMCPMC3216249
OpenAlexW2115188656

What OpenQuestion holds

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LicenceCC BY
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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.