Mutation profile of high‐grade appendiceal mucinous neoplasm

Autor: Xiaoyan Liao, Noam Harpaz, Katherine Sun, Jane Houldsworth, Yansheng Hao, Mark A. Valasek, Xiaodong Li, Alexandros D. Polydorides, Vera Vavinskaya, Ruliang Xu
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
medicine.medical_specialty
Histology
Ataxia Telangiectasia Mutated Proteins
Appendix
Histogenesis
medicine.disease_cause
Gastroenterology
Pathology and Forensic Medicine
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
0302 clinical medicine
Internal medicine
Chromogranins
GTP-Binding Protein alpha Subunits
Gs
medicine
Atypia
GNAS complex locus
Humans
PTEN
Aged
Retrospective Studies
Aged
80 and over
Mutation
biology
business.industry
High-Throughput Nucleotide Sequencing
Sequence Analysis
DNA
General Medicine
Middle Aged
medicine.disease
Adenocarcinoma
Mucinous
Mucinous Neoplasm
030104 developmental biology
medicine.anatomical_structure
Appendiceal Neoplasms
030220 oncology & carcinogenesis
biology.protein
Female
KRAS
Neoplasm Grading
Tumor Suppressor Protein p53
business
Zdroj: Histopathology. 76:461-469
ISSN: 1365-2559
0309-0167
Popis: Aims High-grade appendiceal mucinous neoplasm (HAMN) was recently proposed as a disease entity histologically analogous to low-grade appendiceal mucinous neoplasm (LAMN), but characterised by high-grade cytological atypia. The pathogenesis and clinical features of HAMN have not been fully elucidated. Methods and results Nine cases of HAMN, eight LAMN, 10 appendiceal mucinous adenocarcinomas (MACA) and five appendiceal serrated polyps resected between 2008 and 2017 contributed by three medical centres underwent targeted next-generation sequencing of 50 cancer-related genes. The patients in each category had similar profiles with respect to gender, age, tumour stage and follow-up intervals. Both LAMN and HAMN harboured mutations of KRAS [nine of nine and eight of eight (100%), respectively] and GNAS [five of eight (63%) and five of nine (56%), respectively] in significantly higher proportions than MACA [KRAS, seven of 10 (70%, P = 0.04); GNAS: one of 10 (10%, P = 0.02)] and serrated polyps [KRAS, one of five (20%, P = 0.0007); GNAS: none of five (0%, P = 0.04)]. Four cases of HAMN, but none of LAMN, harboured mutations of TP53 [four of nine (44%)] and/or ATM [two of nine (22%)]. Three cases of HAMN (33%) showed extra-appendiceal spread with retention of the same mutational profiles in the intra- and extra-appendiceal components. The 10 cases of MACA harboured a similar prevalence of TP53 mutations (n = 5, 50%) as HAMN but, unlike LAMN and HAMN, some harboured mutations in PIK3CA, APC, FBXW7, PTEN and SMAD4. Conclusions HAMN and LAMN share high rates of KRAS and GNAS co-mutations supporting a common histogenesis and distinguishing them from MACA. Acquisition of TP53 or ATM mutations by HAMN may drive its progression to a more advanced phenotype.
Databáze: OpenAIRE
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