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PMS2 case studies

PMS2 case studies. Colorectal Cancer Best Practice Training Day 2009. I 1. II 1. II 2. ?. ?. Case 1: background. Male aged 42 (II 2 ) with CRC and Hodgkins lymphoma; MSI high and IHC showed isolated loss of PMS2 expression.

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PMS2 case studies

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  1. PMS2 case studies Colorectal Cancer Best Practice Training Day 2009

  2. I1 II1 II2 ? ? Case 1: background • Male aged 42 (II2) with CRC and Hodgkins lymphoma; MSI high and IHC showed isolated loss of PMS2 expression. • Patient’s mother (I1) affected with endometrial cancer and brother (II2) affected with pancreatic cancer. • DNA from II1 failed to amplify for PCRs above 500bp so only able to report normal results for exons 2-8. • DNA from I1 was subsequently received and amplified successfully for exons 2 and 6-12. (NB exons 11-12 are affected by pseudogene, long PCR is used to get around this problem) • Result: c.1831dupA (p.Ile611fs) identified in exon 11 in I1.

  3. Case 1: reporting I1: • I1 reported as having a mutation, consistent with affected status. Predictive testing offered. • New aliquot of DNA from II1 failed to amplify for long-range PCR. New gene-specific primers designed to amplify shorter fragment (~300bp) surrounding mutation in order to check for mutation in II1. • Result = mutation identified in II1 and reported as consistent with affected status. II1:

  4. Carrier testing requested for parents of two children affected with PNET tumours staining negative for PMS2 Initial testing of exons 6-12 in 2007 showed no mutations Testing of exons 1-5 and MLPA in 2009 found that mum had c.1A>G (p.Met1?) and dad had common variant c.137G>T (p.Ser46Ile) ? ? Case 2: background

  5. Case 2: reporting • c.137G>T (p.Ser46Ile) in the ATPase domain has been found several times in our laboratory and reported in the literature as being associated with colorectal cancers. We report as likely pathogenic. • Mutations found in both parents supports the IHC findings in the children. • Parents are at risk themselves of developing CRC (similar cases reported by Agostini et al, 2005).

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