Evidence for GALNT12 as a moderate penetrance gene for colorectal cancer

Human Mutation
Daniel R EvansKishore Guda

Abstract

Characterizing moderate penetrance susceptibility genes is an emerging frontier in colorectal cancer (CRC) research. GALNT12 is a strong candidate CRC-susceptibility gene given previous linkage and association studies, and inactivating somatic and germline alleles in CRC patients. Previously, we found rare segregating germline GALNT12 variants in a clinic-based cohort (N = 118) with predisposition for CRC. Here, we screened a new population-based cohort of incident CRC cases (N = 479) for rare (MAF ≤1%) deleterious germline GALNT12 variants. GALNT12 screening revealed eight rare variants. Two variants were previously described (p.Asp303Asn, p.Arg297Trp), and additionally, we found six other rare variants: five missense (p.His101Gln, p.Ile142Thr, p.Glu239Gln, p.Thr286Met, p.Val290Phe) and one putative splice-altering variant (c.732-8 G>T). Sequencing of population-matched controls (N = 400) revealed higher burden of these variants in CRC cases compared with healthy controls (P = 0.0381). We then functionally characterized the impact of substitutions on GALNT12 enzyme activity using in vitro-derived peptide substrates. Three of the newly identified GALNT12 missense variants (p.His101Gln, p.Ile142Thr, p.Val290Phe) demonstrated a m...Continue Reading

References

May 1, 1991·Diseases of the Colon and Rectum·H F VasenH T Lynch
Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
Jan 13, 2001·American Journal of Human Genetics·Y PeiP St George-Hyslop
Mar 2, 2002·Science·Anna VelcichLeonard Augenlicht
Aug 14, 2003·Human Molecular Genetics·Proton RahmanNelson B Freimer
Oct 21, 2003·Proceedings of the National Academy of Sciences of the United States of America·Georgia L WiesnerSanford D Markowitz
Feb 19, 2004·Journal of the National Cancer Institute·Asad UmarSudhir Srivastava
Oct 6, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael O WoodsPatrick S Parfrey
May 19, 2006·Cancer Research·Zoe E KempUNKNOWN Colorectal Tumour Gene Identification Study Consortium
Sep 9, 2006·Cell·Kazuaki Ohtsubo, Jamey D Marth
Mar 22, 2007·Journal of the National Cancer Institute·Stavroula RaptisBharati Bapat
Mar 20, 2009·American Journal of Health Behavior·Peizhong Peter WangPatrick S Parfrey
Jul 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kishore GudaSanford D Markowitz
Oct 2, 2009·Surgical Oncology Clinics of North America·Noralane M Lindor
Oct 9, 2009·Nature·Teri A ManolioPeter M Visscher
Jun 17, 2010·Cancer Research·Courtney Gray-McGuireGeorgia L Wiesner
Mar 31, 2012·Human Mutation·Erica ClarkeMichael O Woods
Jun 13, 2012·Nucleic Acids Research·Ngak-Leng SimPauline C Ng
Jan 15, 2013·Current Protocols in Human Genetics·Ivan AdzhubeiShamil R Sunyaev
Jan 19, 2013·The Journal of Biological Chemistry·Duy T Tran, Kelly G Ten Hagen
Jun 12, 2013·Glycobiology·Kirk S B Bergstrom, Lijun Xia
Oct 12, 2013·Human Mutation·Nuria SeguíLaura Valle
Aug 12, 2014·World Journal of Gastroenterology : WJG·Laura Valle
Jan 27, 2015·Annual Review of Pathology·Sean R StowellRichard D Cummings
Apr 29, 2015·Gut and Liver·UNKNOWN Korean Liver Cancer Study Group (KLCSG), UNKNOWN National Cancer Center, Korea (NCC)
Aug 21, 2015·Nature Reviews. Cancer·Salomé S Pinho, Celso A Reis
Dec 17, 2015·European Journal of Human Genetics : EJHG·Guangju ZhaiRoger C Green
Jan 23, 2016·Science Translational Medicine·Eric Vallabh MinikelDaniel G MacArthur
Jun 10, 2016·Cellular Oncology (Dordrecht)·M M HahnA Geurts van Kessel
Jun 15, 2016·Nature Reviews. Clinical Oncology·Nadine TungMark E Robson
Jun 23, 2016·Nature Communications·Daniel ChubbRichard S Houlston
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium

❮ Previous
Next ❯

Citations

Oct 22, 2019·Journal of Cellular and Molecular Medicine·Tianbo GaoTao Wen
Oct 13, 2019·Mutagenesis·Stephanie A SchubertTom van Wezel
Aug 7, 2020·Expert Review of Gastroenterology & Hepatology·Paivi PeltomäkiTaina T Nieminen
Sep 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Amy J FernandezNadine L Samara
Nov 17, 2020·Frontiers in Genetics·Malene DjursbyThomas van Overeem Hansen

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.