Journal article
A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome
R Walker, K Mahmood, JE Joo, M Clendenning, P Georgeson, J Como, S Joseland, SG Preston, Y Antill, R Austin, A Boussioutas, M Bowman, J Burke, A Campbell, S Daneshvar, E Edwards, M Gleeson, A Goodwin, MT Harris, A Henderson Show all
Journal of Translational Medicine | BMC | Published : 2023
Abstract
Routine screening of tumors for DNA mismatch repair (MMR) deficiency (dMMR) in colorectal (CRC), endometrial (EC) and sebaceous skin (SST) tumors leads to a significant proportion of unresolved cases classified as suspected Lynch syndrome (SLS). SLS cases (n = 135) were recruited from Family Cancer Clinics across Australia and New Zealand. Targeted panel sequencing was performed on tumor (n = 137; 80×CRCs, 33×ECs and 24xSSTs) and matched blood-derived DNA to assess for microsatellite instability status, tumor mutation burden, COSMIC tumor mutational signatures and to identify germline and somatic MMR gene variants. MMR immunohistochemistry (IHC) and MLH1 promoter methylation were repeated. I..
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Awarded by National Institutes of Health
Funding Acknowledgements
Funding by a National Health and Medical Research Council of Australia (NHMRC) project Grant GNT1125269 (PI- Daniel Buchanan) supported the design, analysis, and interpretation of data. RW is supported by the Margaret and Irene Stewardson Fund Scholarship and by the Melbourne Research Scholarship. DDB is supported by an NHMRC Investigator grant (GNT1194896), and the University of Melbourne Dame Kate Campbell Fellowship. PG is supported by the University of Melbourne Research Scholarship. MAJ is supported by an NHMRC Investigator grant (GNT1195099). AKW is supported by an NHMRC Investigator grant (GNT1194392). JLH is supported by the University of Melbourne Dame Kate Campbell Fellowship. BP is supported by a Victorian Health and Medical Research Fellowship from the Victorian Government. The Colon Cancer Family Registry (CCFR) was supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under Award Number U01CA167551 and through cooperative agreements from NCI/NIH with the following CCFR centers: Australasian Colorectal Cancer Family Registry (U01 CA074778 and U01/U24 CA097735), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800), Ontario Familial Colorectal Cancer Registry (U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794), University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806), and USC Consortium Colorectal Cancer Family Registry (U01/U24 CA074799). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government, any cancer registry, or the CCFR.