Identification of a novel nucleotide 4803delCC/c.4684delCC mutation and a nucleotide 249T>A/c.130T>A (p.Cys44Ser) mutation in two Greenlandic Inuit families: implications for genetic screening of Greenlandic Inuit families with high risk for breast and/or ovarian cancer

• Published in: Breast Cancer Research and Treatment
• Main Authors: Hansen, Thomas V. O., Jønson, Lars, Albrechtsen, Anders, Steffensen, Ane Y., Bergsten, Eva, Myrhøj, Torben, Ejlertsen, Bent, Nielsen, Finn C.
• Other Authors: Department of Clinical Biochemistry Rigshospitalet, Rigshospitalet Copenhagen, Copenhagen University Hospital-Copenhagen University Hospital, Section of Biostatistics Copenhagen, Department of Public Health Copenhagen, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Department of Oncology, Department of Surgery, Dronning Ingrids Hospital
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2010
• Subjects: Greenland; Inuit; Novel mutation; greenlandic; inuit; inuits
• Online Access: https://hal.archives-ouvertes.fr/hal-00531008; https://hal.archives-ouvertes.fr/hal-00531008/document; https://hal.archives-ouvertes.fr/hal-00531008/file/PEER_stage2_10.1007%252Fs10549-010-0909-9.pdf; https://doi.org/10.1007/s10549-010-0909-9

International audience Germ-line mutations in the tumour suppressor proteins and predispose to breast and ovarian cancer. We have recently identified a Greenlandic Inuit nucleotide 234T>G/c.115T>G (p.Cys39Gly) founder mutation, which at that time was the only disease-causing mutation identified in this population. Here, we describe the identification of a novel disease-causing nucleotide 4803delCC/c.4684delCC mutation in a Greenlandic Inuit with ovarian cancer. The mutation introduces a frameshift and a premature stop at codon 1572. We have also identified a nucleotide 249T>A/c.130T>A (p.Cys44Ser) mutation in another Greenlandic individual with ovarian cancer. This patient share a 1–2 Mb genomic fragment, containing the gene, with four Danish families harbouring the same mutation, suggesting that the 249T>A/c.130T>A (p.Cys44Ser) mutation originates from a Danish ancestor. We conclude that screening of Greenlandic Inuits with high risk of breast or ovarian cancer should include sequencing of the entire gene.