Next generation sequencing to decipher concurrent loss of PMS2 and MSH6 in colorectal cancer

Immunohistochemistry (IHQ) is commonly used for the detection of mismatch repair proteins deficiency (MMRD). One very infrequent abnormal pattern of MMR protein expression is the loss of PMS2 and MSH6, with intact expression of MLH1 and MSH2. We review the frequency of this MMRD IHC pattern among 10...

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Bibliographic Details
Published in:Diagnostic pathology 2020-07, Vol.15 (1), p.84-84, Article 84
Main Authors: Moreno, Esther, Rosa-Rosa, Juan M, Caniego-Casas, Tamara, Ruz-Caracuel, Ignacio, Perna, Cristian, Guillén, Carmen, Palacios, José
Format: Article
Language:English
Subjects:
Adult
Aged
Algorithms
Analysis
Cancer
Cancer therapies
Case Report
Case reports
Chemotherapy
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis
Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
DNA-Binding Proteins - genetics
Endometrial cancer
Endometrium
Female
Gene mutation
Genetic disorders
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Liver
Lynch syndrome
Metastasis
Mismatch repair
Mismatch repair deficiency
Mismatch Repair Endonuclease PMS2 - genetics
MLH1 protein
MMR protein
MSH2 protein
MSH6 protein
Mutation
Next-generation sequencing
NGS
Ovaries
Patients
Protein expression
Proteins
Sequence Analysis, DNA
Tumors
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Summary:Immunohistochemistry (IHQ) is commonly used for the detection of mismatch repair proteins deficiency (MMRD). One very infrequent abnormal pattern of MMR protein expression is the loss of PMS2 and MSH6, with intact expression of MLH1 and MSH2. We review the frequency of this MMRD IHC pattern among 108 colorectal (CRCs) and 35 endometrial cancers in our files with loss of expression of at least one protein, and present two CRCs showing loss of PMS2 and MSH6 protein expression (1.9% of CRCs). NGS analysis of these tumours identified PMS2 mutations (R134* germline mutation in one tumour and M1R and c.1239delA somatic mutation in the other) as the primary event and somatic MSH6 mutation (c.3261dupC) as the secondary event in both tumours. This study suggests that Next Generation Sequencing (NGS) tumour analysis should be considered in the algorithm of Lynch syndrome screening to detect MMR gen somatic mutation in inconclusive cases.
ISSN:1746-1596
1746-1596
DOI:10.1186/s13000-020-01001-2