ArticleJAMA2005
Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer.
Article in JAMA, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Prevalence of pathological germline mutations of hMLH1 and hMSH2 genes in colorectal cancer.PloS one · 2013Pooled it
- Article
- Enhanced clinical assessment of hematologic malignancies through routine paired tumor and normal sequencing.Nature communications · 2023Article
- Genome sequencing identifies complex structural MLH1 variant in unsolved Lynch syndrome.Molecular genetics & genomic medicine · 2023Article
- Whole-genome sequencing identified novel mutations in a Chinese family with lynch syndrome.Frontiers in oncology · 2023Article
- MLH1 intronic variants mapping to + 5 position of splice donor sites lead to deleterious effects on RNA splicing.Familial cancer · 2020Article
- Characterization of a germline splice site variant MLH1 c.678-3T>A in a Lynch syndrome family.Familial cancer · 2020Article
- A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family.Cancer management and research · 2020Article
- RNA analysis of cancer predisposing genes in formalin-fixed paraffin-embedded tissue determines aberrant splicing.European journal of human genetics : EJHG · 2018Article
- Expending Role of Microsatellite Instability in Diagnosis and Treatment of Colorectal Cancers.Journal of gastrointestinal cancer · 2017Review
- A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America.BMC cancer · 2017Article
- A novel heterozygous germline deletion in MSH2 gene in a five generation Chinese family with Lynch syndrome.Oncotarget · 2017Article
- Spectrum of mismatch repair gene mutations and clinical presentation of Hispanic individuals with Lynch syndrome.Cancer genetics · 2017Article
- An Individual with Both MUTYH-Associated Polyposis and Lynch Syndrome Identified by Multi-Gene Hereditary Cancer Panel Testing: A Case Report.Frontiers in genetics · 2016Article
- Review
- Partial duplication of MSH2 spanning exons 7 through 14 in Lynch syndrome.Journal of gastroenterology · 2013Article
- MicroRNA manipulation in colorectal cancer cells: from laboratory to clinical application.Journal of translational medicine · 2012Review
- microRNA expression pattern and its alteration following celecoxib intervention in human colorectal cancer.Experimental and therapeutic medicine · 2012Article
- Prevalence of alterations in DNA mismatch repair genes in patients with young-onset colorectal cancer.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2011Article
- Genetic counseling considerations in the evaluation of families for Lynch syndrome--a review.Journal of genetic counseling · 2011Review
Corrections and comments
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Authors and funding
22 authors at 1 institution in 1 country.
Funding
Abstract
contextThe accurate identification and interpretation of germline mutations in mismatch repair genes in colorectal cancer cases is critical for clinical management. Current data suggest that mismatch repair mutations are highly heterogeneous and that many mutations are not detected when conventional DNA sequencing alone is used.
objectiveTo evaluate the potential of conversion analysis compared with DNA sequencing alone to detect heterogeneous germline mutations in MLH1, MSH2, and MSH6 in colorectal cancer patients. DESIGN, SETTING, AND
participantsMulticenter study with patients who participate in the Colon Cancer Family Registry. Mutation analyses were performed in participant samples determined to have a high probability of carrying mismatch repair germline mutations. Samples from a total of 64 hereditary nonpolyposis colorectal cancer cases, 8 hereditary nonpolyposis colorectal cancer-like cases, and 17 cases diagnosed prior to age 50 years were analyzed from June 2002 to June 2003.
main outcome measuresClassification of family members as carriers or noncarriers of germline mutations in MLH1, MSH2, or MSH6; mutation data from conversion analysis compared with genomic DNA sequencing.
resultsGenomic DNA sequencing identified 28 likely deleterious exon mutations, 4 in-frame deletion mutations, 16 missense changes, and 22 putative splice site mutations. Conversion analysis identified all mutations detected by genomic DNA sequencing--plus an additional exon mutation, 12 large genomic deletions, and 1 exon duplication mutation--yielding an increase of 33% (14/42) in diagnostic yield of deleterious mutations. Conversion analysis also showed that 4 of 16 missense changes resulted in exon skipping in transcripts and that 17 of 22 putative splice site mutations affected splicing or mRNA transcript stability. Conversion analysis provided an increase of 56% (35/63) in the diagnostic yield of genetic testing compared with genomic DNA sequencing alone.
conclusionsThe data confirm the heterogeneity of mismatch repair mutations and reveal that many mutations in colorectal cancer cases would be missed using conventional genomic DNA sequencing alone. Conversion analysis substantially increases the diagnostic yield of genetic testing for mismatch repair mutations in patients diagnosed as having colorectal cancer.
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