Mutation profile of high-grade appendiceal mucinous neoplasm.
Adenocarcinoma, Mucinous
/ genetics
Adult
Aged
Aged, 80 and over
Appendiceal Neoplasms
/ genetics
Appendix
/ pathology
Ataxia Telangiectasia Mutated Proteins
/ genetics
Chromogranins
/ genetics
Female
GTP-Binding Protein alpha Subunits, Gs
/ genetics
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Neoplasm Grading
Proto-Oncogene Proteins p21(ras)
/ genetics
Retrospective Studies
Sequence Analysis, DNA
Tumor Suppressor Protein p53
/ genetics
appendix
high-grade appendiceal mucinous neoplasm
next-generation sequencing
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
23
05
2019
revised:
02
09
2019
accepted:
06
09
2019
pubmed:
7
9
2019
medline:
27
10
2020
entrez:
7
9
2019
Statut:
ppublish
Résumé
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. 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. 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.
Substances chimiques
Chromogranins
0
KRAS protein, human
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
ATM protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
GNAS protein, human
EC 3.6.1.-
GTP-Binding Protein alpha Subunits, Gs
EC 3.6.5.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
461-469Informations de copyright
© 2019 John Wiley & Sons Ltd.
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