Evidence map›Paper›PMID 29075860›Full record

ArticleWorld journal of surgery2018

DNA Mismatch Repair Deficiency Promotes Genomic Instability in a Subset of Papillary Thyroid Cancers.

Mahsa Javid, Thanyawat Sasanakietkul, Norman G Nicolson, Courtney E Gibson, Glenda G Callender, Reju Korah, Tobias Carling

Abstract read
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In one paragraph

Article in World journal of surgery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

11 citing papers in PubMed, 18 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

7 authors at 1 institution in 1 country.

Mahsa JavidYale Endocrine Neoplasia Laboratory, Section of Endocrine Surgery, Department of Surgery, Yale University School of Medicine, PO Box 208062, FMB 130A, New Haven, CT, 06520-8062, USA.
Thanyawat SasanakietkulYale Endocrine Neoplasia Laboratory, Section of Endocrine Surgery, Department of Surgery, Yale University School of Medicine, PO Box 208062, FMB 130A, New Haven, CT, 06520-8062, USA.
Norman G NicolsonYale Endocrine Neoplasia Laboratory, Section of Endocrine Surgery, Department of Surgery, Yale University School of Medicine, PO Box 208062, FMB 130A, New Haven, CT, 06520-8062, USA.
Courtney E GibsonYale Endocrine Neoplasia Laboratory, Section of Endocrine Surgery, Department of Surgery, Yale University School of Medicine, PO Box 208062, FMB 130A, New Haven, CT, 06520-8062, USA.
Glenda G CallenderYale Endocrine Neoplasia Laboratory, Section of Endocrine Surgery, Department of Surgery, Yale University School of Medicine, PO Box 208062, FMB 130A, New Haven, CT, 06520-8062, USA.
Reju KorahYale Endocrine Neoplasia Laboratory, Section of Endocrine Surgery, Department of Surgery, Yale University School of Medicine, PO Box 208062, FMB 130A, New Haven, CT, 06520-8062, USA.
Tobias CarlingYale Endocrine Neoplasia Laboratory, Section of Endocrine Surgery, Department of Surgery, Yale University School of Medicine, PO Box 208062, FMB 130A, New Haven, CT, 06520-8062, USA. tobias.carling@yale.edu.
Yale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEfficient DNA damage repair by MutL-homolog DNA mismatch repair (MMR) enzymes, MLH1, MLH3, PMS1 and PMS2, are required to maintain thyrocyte genomic integrity. We hypothesized that persistent oxidative stress and consequent transcriptional dysregulation observed in thyroid follicles will lead to MMR deficiency and potentiate papillary thyroid tumorigenesis.

methodsMMR gene expression was analyzed by targeted microarray in 18 papillary thyroid cancer (PTC), 9 paracarcinoma normal thyroid (PCNT) and 10 normal thyroid (NT) samples. The findings were validated by qRT-PCR, and in follicular thyroid cancers (FTC) and follicular thyroid adenomas (FTA) for comparison. FOXO transcription factor expression was also analyzed. Protein expression was assessed by immunohistochemistry. Genomic integrity was evaluated by whole-exome sequencing-derived read-depth analysis and Mann-Whitney U test. Clinical correlations were assessed using Fisher's exact and t tests.

resultsMicroarray and qRT-PCR revealed reduced expression of all four MMR genes in PTC compared with PCNT and of PMS2 compared with NT. FTC and FTA showed upregulation in MLH1, MLH3 and PMS2. PMS2 protein expression correlated with the mRNA expression pattern. FOXO1 showed lower expression in PMS2-deficient PTCs (log2-fold change -1.72 vs. -0.55, U = 11, p < 0.05 two-tailed). Rate of LOH, a measure of genomic instability, was higher in PMS2-deficient PTCs (median 3 and 1, respectively; U = 26, p < 0.05 two-tailed). No correlation was noted between MMR deficiency and clinical characteristics.

conclusionsMMR deficiency, potentially promoted by FOXO1 suppression, may explain the etiology for PTC development in some patients. FTC and FTA retain MMR activity and are likely caused by a different tumorigenic pathway.

Indexed as

DNA Mismatch RepairGenomic InstabilityAdenomaAdolescentAdultAgedAged, 80 and overCarcinoma, PapillaryDNA-Binding ProteinsDNA Repair EnzymesFemaleForkhead Box Protein O1HumansImmunohistochemistryMaleMiddle AgedDNA-Binding ProteinsDNA Repair EnzymesForkhead Box Protein O1FOXO1 protein, human

Identifiers

PMID29075860
OpenAlexW2761320987

What OpenQuestion holds

Textmetadata
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.