The genetic profile and molecular subtypes of human pseudomyxoma peritonei and appendiceal mucinous neoplasms: a systematic review
The genetic profile and molecular subtypes of human pseudomyxoma peritonei and appendiceal mucinous neoplasms: a systematic review
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38–100%), GNAS (17–100%), and TP53 (5–23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial. Graphical Abstract: [Figure not available: see fulltext.]
Appendiceal mucinous neoplasms, GNAS, KRAS, Pseudomyxoma peritonei, Somatic gene mutations, Survival
335-359
Murage, Nora Wangari
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Ahmed, Nada Mabrouk
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Underwood, Timothy J
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Walters, Zoë S
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Breininger, Stella Panagio
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March 2023
Murage, Nora Wangari
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Ahmed, Nada Mabrouk
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Underwood, Timothy J
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Walters, Zoë S
e1ccd35d-63a9-4951-a5da-59122193740d
Breininger, Stella Panagio
b6027df8-22a3-4d09-8799-6d14123f9ce4
Murage, Nora Wangari, Ahmed, Nada Mabrouk, Underwood, Timothy J, Walters, Zoë S and Breininger, Stella Panagio
(2023)
The genetic profile and molecular subtypes of human pseudomyxoma peritonei and appendiceal mucinous neoplasms: a systematic review.
Cancer and Metastasis Reviews, 42 (1), .
(doi:10.1007/s10555-023-10088-0).
Abstract
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38–100%), GNAS (17–100%), and TP53 (5–23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial. Graphical Abstract: [Figure not available: see fulltext.]
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s10555-023-10088-0
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Accepted/In Press date: 20 January 2023
e-pub ahead of print date: 1 February 2023
Published date: March 2023
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© 2023, The Author(s).
Keywords:
Appendiceal mucinous neoplasms, GNAS, KRAS, Pseudomyxoma peritonei, Somatic gene mutations, Survival
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Local EPrints ID: 475742
URI: http://eprints.soton.ac.uk/id/eprint/475742
ISSN: 0167-7659
PURE UUID: 79506b59-05a3-4da9-8f5d-c36815b57eb1
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Date deposited: 27 Mar 2023 16:45
Last modified: 17 Mar 2024 03:48
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Author:
Nora Wangari Murage
Author:
Nada Mabrouk Ahmed
Author:
Stella Panagio Breininger
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