Evidence map›Paper›PMID 19075190›Full record

ArticleBlood2009

High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients.

Jeffrey W Tyner, Heidi Erickson, Michael W N Deininger, Stephanie G Willis, Christopher A Eide, Ross L Levine, Michael C Heinrich, Norbert Gattermann, D Gary Gilliland, Brian J Druker and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

68 citing papers in PubMed, 134 citations in OpenAlex.

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8 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 2 countries.

Jeffrey W TynerDivision of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland, OR 97239, USA
Heidi Erickson
Michael W N Deininger
Stephanie G Willis
Christopher A Eide
Ross L Levine
Michael C Heinrich
Norbert Gattermann
D Gary Gilliland
Brian J Druker
Marc M Loriaux
Oregon Health & Science University · USHoward Hughes Medical Institute · USHeinrich Heine University Düsseldorf · DE

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Transforming mutations in NRAS and KRAS are thought to play a causative role in the development of numerous cancers, including myeloid malignancies. Although mutations at amino acids 12, 13, or 61 account for the majority of oncogenic Ras variants, we hypothesized that less frequent mutations at alternate residues may account for disease in some patients with cancer of unexplained genetic etiology. To search for additional, novel RAS mutations, we sequenced all coding exons in NRAS, KRAS, and HRAS in 329 acute myeloid leukemia (AML) patients, 32 chronic myelomonocytic leukemia (CMML) patients, and 96 healthy individuals. We detected 4 "noncanonical" point mutations in 7 patients: N-Ras(G60E), K-Ras(V14I), K-Ras(T74P), and K-Ras(A146T). All 4 Ras mutants exhibited oncogenic properties in comparison with wild-type Ras in biochemical and functional assays. The presence of transforming RAS mutations outside of positions 12, 13, and 61 reveals that alternate mechanisms of transformation by RAS may be overlooked in screens designed to detect only the most common RAS mutations. Our results suggest that RAS mutations may play a greater role in leukemogenesis than currently believed and indicate that high-throughput screening for mutant RAS alleles in cancer should include analysis of the entire RAS coding region.

Indexed as

Point MutationAnimalsBone Marrow CellsCell LineCell Transformation, NeoplasticFibroblastsGenetic TestingHumansLeukemia, Myeloid, AcuteLeukemia, Myelomonocytic, ChronicMiceMice, Inbred BALB CProto-Oncogene Proteins p21(ras)Signal TransductionProto-Oncogene Proteins p21(ras)

Identifiers

PMID19075190
PMCPMC2647674
OpenAlexW1981125188

What OpenQuestion holds

Textmetadata
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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.