Detection of large scale 3′ deletions in the PMS2 gene amongst Colon-CFR participants: have we been missing anything?
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Current screening practices have been able to identify PMS2 mutations in 78 % of cases of colorectal cancer from the Colorectal Cancer Family Registry (Colon CFR) which showed solitary loss of the PMS2 protein. However the detection of large-scale deletions in the 3′ end of the PMS2 gene has not been possible due to technical difficulties associated with pseudogene sequences. Here, we utilised a recently described MLPA/long-range PCR-based approach to screen the remaining 22 % (n = 16) of CRC-affected probands for mutations in the 3′ end of the PMS2 gene. No deletions encompassing any or all of exons 12 through 15 were identified; therefore, our results suggest that 3′ deletions in PMS2 are not a frequent occurrence in such families.
KeywordsLynch syndrome PMS2 Germline testing Large deletions Pseudogenes Colorectal cancer
The authors thank all study participants of the Colon Cancer Family Registry and study co-coordinators and technical staff for their contributions to this project, in particular Judi Maskiell, Belinda Nagler, Sally-Ann Pearson, Rhiannon Walters, David Packenas and Erika Pavluk and participant interviewers for their contributions to this project. We thank individual participants in the study who made this work possible and the contribution of the Jeremy Jass Memorial Pathology Collection. This work was supported by the National Cancer Institute, National Institutes of Health under RFA #CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and Principal Investigators. Collaborating centres include Australasian Colorectal Cancer Family Registry (U01 CA097735), Familial Colorectal Neoplasia Collaborative Group (U01 CA074799) [USC], Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794), and University of Hawaii Colorectal Cancer Family Registry (U01 CA074806). MAJ is an NHMRC Senior Research Fellow. JLH is an NHMRC Australia Fellow. During this work JY was supported by a Cancer Council Queensland Senior Research Fellowship.
Conflict of interest
The authors have no conflict of interest to declare with respect to this manuscript.
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