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.
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,...
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doaj-3e880ba13c9140f9962856f4f8dc8fd22020-11-25T00:43:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01138e020305210.1371/journal.pone.0203052A novel panel of short mononucleotide repeats linked to informative polymorphisms enabling effective high volume low cost discrimination between mismatch repair deficient and proficient tumours.Lisa RedfordGhanim AlhilalStephanie NeedhamOttie O'BrienJulie CoakerJohn TysonLeonardo Maldaner AmorimIona MiddletonOsagi IzuoguMark ArendsAnca OniscuÁngel Miguel AlonsoSira Moreno LagunaRichard GallonHarsh ShethMauro Santibanez-KorefMichael S JacksonJohn BurnSomatic 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 a reliable, scalable routine test for MSI.http://europepmc.org/articles/PMC6114912?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lisa Redford Ghanim Alhilal Stephanie Needham Ottie O'Brien Julie Coaker John Tyson Leonardo Maldaner Amorim Iona Middleton Osagi Izuogu Mark Arends Anca Oniscu Ángel Miguel Alonso Sira Moreno Laguna Richard Gallon Harsh Sheth Mauro Santibanez-Koref Michael S Jackson John Burn |
spellingShingle |
Lisa Redford Ghanim Alhilal Stephanie Needham Ottie O'Brien Julie Coaker John Tyson Leonardo Maldaner Amorim Iona Middleton Osagi Izuogu Mark Arends Anca Oniscu Ángel Miguel Alonso Sira Moreno Laguna Richard Gallon Harsh Sheth Mauro Santibanez-Koref Michael S Jackson John Burn 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 |
author_facet |
Lisa Redford Ghanim Alhilal Stephanie Needham Ottie O'Brien Julie Coaker John Tyson Leonardo Maldaner Amorim Iona Middleton Osagi Izuogu Mark Arends Anca Oniscu Ángel Miguel Alonso Sira Moreno Laguna Richard Gallon Harsh Sheth Mauro Santibanez-Koref Michael S Jackson John Burn |
author_sort |
Lisa Redford |
title |
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. |
title_short |
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. |
title_full |
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. |
title_fullStr |
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. |
title_full_unstemmed |
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. |
title_sort |
novel panel of short mononucleotide repeats linked to informative polymorphisms enabling effective high volume low cost discrimination between mismatch repair deficient and proficient tumours. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2018-01-01 |
description |
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 a reliable, scalable routine test for MSI. |
url |
http://europepmc.org/articles/PMC6114912?pdf=render |
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