TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer

Abstract Targeted sequencing for somatic mutations across the hotspots of 50 cancer-related genes was performed using biopsy specimens to investigate whether clinicopathological factors and genomic alterations correlated with prognosis in locally advanced cervical cancer. Seventy patients diagnosed...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ikumi Kuno, Daisuke Takayanagi, Yuka Asami, Naoya Murakami, Maiko Matsuda, Yoko Shimada, Sou Hirose, Mayumi Kobayashi Kato, Masaaki Komatsu, Ryuji Hamamoto, Kae Okuma, Takashi Kohno, Jun Itami, Hiroshi Yoshida, Kouya Shiraishi, Tomoyasu Kato
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01be47dd8ca541d2a942cb3061a4dbb3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:01be47dd8ca541d2a942cb3061a4dbb3
record_format	dspace
spelling	oai:doaj.org-article:01be47dd8ca541d2a942cb3061a4dbb32021-12-02T19:17:05ZTP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer10.1038/s41598-021-98527-22045-2322https://doaj.org/article/01be47dd8ca541d2a942cb3061a4dbb32021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98527-2https://doaj.org/toc/2045-2322Abstract Targeted sequencing for somatic mutations across the hotspots of 50 cancer-related genes was performed using biopsy specimens to investigate whether clinicopathological factors and genomic alterations correlated with prognosis in locally advanced cervical cancer. Seventy patients diagnosed with International Federation of Obstetrics and Gynecology (FIGO) stage III to IVA cervical cancer underwent radiotherapy or concurrent chemoradiotherapy at the National Cancer Center Hospital between January 2008 and December 2017. Mutations were detected in 47 of 70 [67% of cases; frequency of genetic alterations was as follows: PIK3CA (51%), FBXW7 (10%), PTEN (7.1%), and TP53 (5.7%)]. The Cancer Genome Atlas (TCGA) datasets showed a similar distribution of somatic mutations, but PIK3CA mutation frequency was significantly higher in our cohort than in TCGA datasets (P = 0.028). Patients with TP53 mutation were significantly related to poor progression-free survival (PFS) (hazard ratio [HR] = 3.53, P = 0.042). Patients with tumor diameters > 70 mm were associated with poor prognosis (HR = 2.96, P = 0.0048). Patients with non-HPV16/18 genotypes had worse prognosis than those with HPV16/18 genotypes (HR = 2.15, P = 0.030). Hence, patients with locally advanced cervical cancer, TP53 mutation, large tumor diameter, and non-HPV16/18 genotype were independently correlated with poor PFS, despite concurrent chemoradiotherapy.Ikumi KunoDaisuke TakayanagiYuka AsamiNaoya MurakamiMaiko MatsudaYoko ShimadaSou HiroseMayumi Kobayashi KatoMasaaki KomatsuRyuji HamamotoKae OkumaTakashi KohnoJun ItamiHiroshi YoshidaKouya ShiraishiTomoyasu KatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ikumi Kuno Daisuke Takayanagi Yuka Asami Naoya Murakami Maiko Matsuda Yoko Shimada Sou Hirose Mayumi Kobayashi Kato Masaaki Komatsu Ryuji Hamamoto Kae Okuma Takashi Kohno Jun Itami Hiroshi Yoshida Kouya Shiraishi Tomoyasu Kato TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer
description	Abstract Targeted sequencing for somatic mutations across the hotspots of 50 cancer-related genes was performed using biopsy specimens to investigate whether clinicopathological factors and genomic alterations correlated with prognosis in locally advanced cervical cancer. Seventy patients diagnosed with International Federation of Obstetrics and Gynecology (FIGO) stage III to IVA cervical cancer underwent radiotherapy or concurrent chemoradiotherapy at the National Cancer Center Hospital between January 2008 and December 2017. Mutations were detected in 47 of 70 [67% of cases; frequency of genetic alterations was as follows: PIK3CA (51%), FBXW7 (10%), PTEN (7.1%), and TP53 (5.7%)]. The Cancer Genome Atlas (TCGA) datasets showed a similar distribution of somatic mutations, but PIK3CA mutation frequency was significantly higher in our cohort than in TCGA datasets (P = 0.028). Patients with TP53 mutation were significantly related to poor progression-free survival (PFS) (hazard ratio [HR] = 3.53, P = 0.042). Patients with tumor diameters > 70 mm were associated with poor prognosis (HR = 2.96, P = 0.0048). Patients with non-HPV16/18 genotypes had worse prognosis than those with HPV16/18 genotypes (HR = 2.15, P = 0.030). Hence, patients with locally advanced cervical cancer, TP53 mutation, large tumor diameter, and non-HPV16/18 genotype were independently correlated with poor PFS, despite concurrent chemoradiotherapy.
format	article
author	Ikumi Kuno Daisuke Takayanagi Yuka Asami Naoya Murakami Maiko Matsuda Yoko Shimada Sou Hirose Mayumi Kobayashi Kato Masaaki Komatsu Ryuji Hamamoto Kae Okuma Takashi Kohno Jun Itami Hiroshi Yoshida Kouya Shiraishi Tomoyasu Kato
author_facet	Ikumi Kuno Daisuke Takayanagi Yuka Asami Naoya Murakami Maiko Matsuda Yoko Shimada Sou Hirose Mayumi Kobayashi Kato Masaaki Komatsu Ryuji Hamamoto Kae Okuma Takashi Kohno Jun Itami Hiroshi Yoshida Kouya Shiraishi Tomoyasu Kato
author_sort	Ikumi Kuno
title	TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer
title_short	TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer
title_full	TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer
title_fullStr	TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer
title_full_unstemmed	TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer
title_sort	tp53 mutants and non-hpv16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/01be47dd8ca541d2a942cb3061a4dbb3
work_keys_str_mv	AT ikumikuno tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT daisuketakayanagi tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT yukaasami tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT naoyamurakami tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT maikomatsuda tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT yokoshimada tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT souhirose tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT mayumikobayashikato tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT masaakikomatsu tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT ryujihamamoto tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT kaeokuma tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT takashikohno tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT junitami tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT hiroshiyoshida tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT kouyashiraishi tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer AT tomoyasukato tp53mutantsandnonhpv1618genotypesarepoorprognosticfactorsforconcurrentchemoradiotherapyinlocallyadvancedcervicalcancer
_version_	1718376894343151616

TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer

Ejemplares similares