常见的PanNETs-胰腺神经内分泌肿瘤的全基因组图谱nature.pptVIP

Whole-genome landscape of pancreatic neuroendocrine tumours《NATURE》 师煜 井佳瑜 PanNETs Pancreatic neuroendocrine tumours (PanNETs) ：the second most common epithelial neoplasm of the pancreas and have a mortality rate of 60%. WHO classification： low grade (G1), intermediate grade (G2), high grade (G3) G3 tumours are invariably lethal 90% of PanNETs are grade G1 or G2 PanNETs PanNETs: sporadic, three hereditary syndromes: multiple endocrine neoplasia type 1 (MEN-1), von Hippel-Lindau syndrome (VHL), and occasionally tuberous sclerosis complex (TSC) MEN-1: 35% of PanNETs mTOR signalling: 14% of patients , Everolimus(advanced PanNET) apoptotic regulator DAXX or the chromatin modifier ATRX: 40% of PanNETs, promote alternative lengthening of telomeres (ALT,端粒替代延长机制) and chromosomal instability PanNETs 102 clinically sporadic PanNETs：candidate mechanisms that activate mTOR signalling We have uncovered an important role for germline MUTYH variants In addition, we have identified a larger-than-anticipated germline contri- bution to clinically sporadic PanNETs, delineating future challenges in the clinical assessment of susceptibility. Genomic landscape of PanNETs Patients were recruited and consent for genomic sequencing obtained as part of the International Cancer Genome Consortium (). All cases were classified according to WHO criteria 98 resected PanNETs : 36 tumours classified as G1, 57 as G2, and 5 as G3. Four additional PanNETs and one colon cancer from a patient with MUTYH-associated polyposis (MAP) were sequenced to validate mutational signatures. Genomic landscape of PanNETs Mutational mechanisms in PanNET lower mutation burden than exocrine counterpart Five signatures (A–E) : A: MUTYH B: APOBEC (minimal) C: BRCA ( breast, pancreatic ductal, ovarian and oesophageal carcinomas) D: Age (deamination) E: signature 5 (unknown) Validation of MUTYH signature in four additional PanNETs and one colon tumour. Thr