A novel panel of short mononucleotide repeats linked to informative polymorphisms enabling effective high volume low cost discrimination between mismatch repair deficient and proficient tumours

PloS One
Lisa RedfordJohn Burn

Abstract

Somatic mutations in mononucleotide repeats are commonly used to assess the mismatch repair status of tumours. Current tests focus on repeats with a length above 15bp, which tend to be somatically more unstable than shorter ones. These longer repeats also have a substantially higher PCR error rate, and tests that use capillary electrophoresis for fragment size analysis often require expert interpretation. In this communication, we present a panel of 17 short repeats (length 7-12bp) for sequence-based microsatellite instability (MSI) testing. Using a simple scoring procedure that incorporates the allelic distribution of the mutant repeats, and analysis of two cohort of tumours totalling 209 samples, we show that this panel is able to discriminate between MMR proficient and deficient tumours, even when constitutional DNA is not available. In the training cohort, the method achieved 100% concordance with fragment analysis, while in the testing cohort, 4 discordant samples were observed (corresponding to 97% concordance). Of these, 2 showed discrepancies between fragment analysis and immunohistochemistry and one was reclassified after re-testing using fragment analysis. These results indicate that our approach offers the option of ...Continue Reading

References

Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
Mar 29, 2001·The Journal of Molecular Diagnostics : JMD·K D BergJ R Eshleman
Apr 5, 2002·Genome Research·W James Kent
Feb 19, 2004·Journal of the National Cancer Institute·Asad UmarSudhir Srivastava
Jan 22, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S PopatR S Houlston
Dec 29, 2006·Cancer Biomarkers : Section a of Disease Markers·Darryl Shibata
Jun 19, 2007·Cancer Research·Heli SammalkorpiLauri A Aaltonen
Apr 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Pia AlhopuroLauri A Aaltonen
Sep 24, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Heather HampelAlbert de la Chapelle
Jan 7, 2009·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Glenn E PalomakiStephen N Thibodeau
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Apr 28, 2010·Gastroenterology·C Richard Boland, Ajay Goel
Jun 3, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Albert de la Chapelle, Heather Hampel
Sep 1, 2011·Annals of Surgical Oncology·Guillaume CanardYann Parc
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Oct 24, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christoph EngelHans F A Vasen
Dec 18, 2012·Genome Biology and Evolution·Guruprasad AnandaKateryna D Makova
Mar 1, 2014·Archives of Pathology & Laboratory Medicine·Theresa A BoyleUNKNOWN College of American Pathologists Molecular Oncology Committee
Jul 6, 2014·Clinical Chemistry·Stephen J SalipanteColin C Pritchard
Sep 18, 2014·The American Journal of Surgical Pathology·Anne M MillsTeri A Longacre
Sep 23, 2014·Health Technology Assessment : HTA·Tristan SnowsillChris Hyde
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Aug 8, 2015·Gastroenterology·Rodrigo Santa Cruz GuindaliniSonia S Kupfer
Jun 9, 2016·Genome Biology·William McLarenFiona Cunningham
Oct 3, 2017·Bioinformatics·Mark F RogersColin Campbell
Dec 27, 2017·The Journal of Molecular Diagnostics : JMD·Lizhen ZhuYing Yuan
Feb 10, 2018·International Journal of Cancer. Journal International Du Cancer·Aysel AhadovaMatthias Kloor
Feb 24, 2018·Journal of Clinical Pathology·Susanti SusantiMohammad Ilyas
Jan 1, 2017·JCO Precision Oncology·Russell BonnevilleSameek Roychowdhury

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Datasets Mentioned

BETA
PRJEB27681
ERS2623574

Methods Mentioned

BETA
electrophoresis
PCR
exome sequencing

Software Mentioned

GATK
GATK UnifiedGenotyper
custom
R scripts
Perl
CADD
PICARD
Samtools
BWA
Fastq

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