Evidence map›Paper›PMID 19190129›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009

Distinct BRAF (V600E) and KRAS mutations in high microsatellite instability sporadic colorectal cancer in African Americans.

Krishan Kumar, Hassan Brim, Francis Giardiello, Duane T Smoot, Mehdi Nouraie, Edward L Lee, Hassan Ashktorab

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 2 pooled it
3.9field-weighted citation impact, top 7% 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

45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.

  1. Pooled it
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  15. Genomics of Colorectal Cancer in African Americans.Next generation, sequencing & applications · 2016
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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 2 institutions in 1 country.

Krishan KumarDepartment of Medicine and Cancer Center, Howard University, Washington, District of Columbia 20060, USA.
Hassan Brim
Francis Giardiello
Duane T Smoot
Mehdi Nouraie
Edward L Lee
Hassan Ashktorab
Howard University · USJohns Hopkins University · US

Funding

Tumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI LENNON, ANNE MARIE · 1993 to 2022
$54.6M
METHYLATION PROFILING AND RISK OF COLORECTAL CANCERR01CA102681 · NCI · HOWARD UNIVERSITY · PI ASHKTORAB, HASSAN · 2003 to 2007
$1.5M
NCI NIH HHS CA102681NCI NIH HHS P50 CA062924NCI NIH HHS R01 CA102681
6 · The paper itself

Abstract

purposeColorectal cancer develops through genetic, epigenetic, and environmental events that result in uncontrolled cell proliferation. Colorectal cancer incidence and mortality is higher in African Americans (AA) than in the general population. Here, we carried out a molecular analysis of sporadic colorectal cancer tumors from AAs to investigate possible explanations for the observed disparities. EXPERIMENTAL

designA total of 222 AA colorectal cancer tumors were analyzed for microsatellite instability (MSI) for protein expression of two DNA mismatch repair genes, MLH1 and MSH2, by immunohistochemistry; for the methylation silencing of MLH1, p16, APC, and APC2 promoters by methylation-specific PCR; and for point mutations in two oncogenes, KRAS and BRAF, by sequencing.

resultsIn our sample, 19.8% of the AAs colorectal cancer tumors were MSI high (MSI-H) and did not associate with any of the clinicopathologic features, except tumor differentiation. Higher levels of inactive DNA mismatch repair proteins MLH1 (41%) and MSH2 (33%) were found by immunohistochemistry. Methylation-specific PCR analysis revealed a high level of methylation for MLH1 (66%), APC (53%), and APC2 (90%), but not for p16 (26%). BRAF mutations were only within the MSI-H tumors, whereas most (64%) of KRAS mutations were found within the non-MSI-H group.

conclusionsMLH1, MSH2, and BRAF alterations are significantly associated with MSI-H phenotype, unlike APC, APC2 and KRAS alterations. The prominent role of DNA mismatch repair gene suppression in MSI-H and a distinctive role of BRAF and KRAS mutations with respect to MSI status are supported by this study.

Indexed as

Microsatellite InstabilityMutationAdaptor Proteins, Signal TransducingAdultAgedBlack or African AmericanColorectal NeoplasmsDNA MethylationFemaleGenes, APCGenes, p16HumansMaleMiddle AgedMutL Protein Homolog 1MutS Homolog 2 ProteinAdaptor Proteins, Signal TransducingBRAF protein, humanKRAS protein, humanMLH1 protein, humanMSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinNuclear ProteinsProto-Oncogene ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)ras Proteins

Identifiers

PMID19190129
PMCPMC2713502
OpenAlexW2157785921

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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.