Details

Autor(en) / Beteiligte

• Georgeson, Peter
• Harrison, Tabitha A
• Pope, Bernard J
• Zaidi, Syed H
• Qu, Conghui
• Steinfelder, Robert S
• Lin, Yi
• Joo, Jihoon E
• Mahmood, Khalid
• Clendenning, Mark
• Walker, Romy
• Amitay, Efrat L
• Berndt, Sonja I
• Brenner, Hermann
• Campbell, Peter T
• Cao, Yin
• Chan, Andrew T
• Chang-Claude, Jenny
• Doheny, Kimberly F
• Drew, David A
• Figueiredo, Jane C
• French, Amy J
• Gallinger, Steven
• Giannakis, Marios
• Giles, Graham G
• Gsur, Andrea
• Gunter, Marc J
• Hoffmeister, Michael
• Hsu, Li
• Huang, Wen-Yi
• Limburg, Paul
• Manson, JoAnn E
• Moreno, Victor
• Nassir, Rami
• Nowak, Jonathan A
• Obón-Santacana, Mireia
• Ogino, Shuji
• Phipps, Amanda I
• Potter, John D
• Schoen, Robert E
• Sun, Wei
• Toland, Amanda E
• Trinh, Quang M
• Ugai, Tomotaka
• Macrae, Finlay A
• Rosty, Christophe
• Hudson, Thomas J
• Jenkins, Mark A
• Thibodeau, Stephen N
• Winship, Ingrid M
• Peters, Ulrike
• Buchanan, Daniel D

Titel

Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures

Ist Teil von

• Nature communications, 2022-06, Vol.13 (1), p.3254-3254, Article 3254

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and matched germline targeted multi-gene panel approach, our classifier identifies all biallelic MUTYH carriers and all known non-carriers in an independent test set of 3019 colorectal cancers (accuracy = 100% (95% confidence interval 99.87-100%)). All monoallelic MUTYH carriers are classified with the non-MUTYH carriers. The classifier provides evidence for a pathogenic classification for two VUS and a benign classification for five VUS. Somatic hotspot mutations KRAS p.G12C and PIK3CA p.Q546K are associated with colorectal cancers from biallelic MUTYH carriers compared with non-carriers (p = 2 × 10 and p = 6 × 10 , respectively). Here, we demonstrate the potential application of mutational signatures to tumor sequencing workflows to improve the identification of biallelic MUTYH carriers.