Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

被引：13

作者：

Fernandez-Mateos, Javier ^{[1
,2
,3
,4
]}

Perez-Garcia, Jessica ^{[3
,4
]}

Seijas-Tamayo, Raquel ^{[1
,2
]}

Mesia, Ricard ^{[5
]}

Rubio-Casadevall, Jordi ^{[6
]}

Garcia-Giron, Carlos ^{[7
]}

Iglesias, Lara ^{[8
]}

Carral Maseda, Alberto ^{[9
]}

Adansa Klain, Juan Carlos ^{[1
,2
]}

Taberna, Miren ^{[5
]}

Vazquez, Silvia ^{[5
]}

Asuncion Gomez, Maria ^{[10
]}

del Barco, Edel ^{[1
,2
]}

Ocana, Alberto ^{[11
,12
]}

Gonzalez-Sarmiento, Rogelio ^{[2
,3
,4
]}

Jesus Cruz-Hernandez, Juan ^{[1
,2
,3
,4
]}

机构：

[1] Univ Hosp Salamanca, Med Oncol Serv, IBSAL, Salamanca 37007, Spain

[2] Univ Salamanca, Biomed Res Inst Salamanca IBSAL, CSIC, SACYL, Salamanca 37007, Spain

[3] Univ Salamanca, Dept Med, Mol Med Unit IBSAL, Salamanca 37007, Spain

[4] Univ Salamanca, Inst Mol & Cellular Biol Canc IBMCC, CSIC, Salamanca 37007, Spain

[5] Univ Barcelona, IDIBELL, Inst Catala Oncol, Med Oncol Dept, Barcelona 08908, Spain

[6] Inst Catala Oncol, Med Oncol Serv, Girona 17007, Spain

[7] Hosp Univ Burgos, Med Oncol Serv, Burgos 09006, Spain

[8] Hosp Univ 12 Octubre, Med Oncol Serv, Madrid 28041, Spain

[9] Hosp Univ Lucus Augusti, Med Oncol Serv, Lugo 27003, Spain

[10] Univ Hosp Salamanca, Pathologist Serv, Salamanca 37007, Spain

[11] Hosp Clin San Carlos, CIBERONC, IdISSC, Madrid 28040, Spain

[12] Univ Castilla La Mancha, Ctr Reg Invest Biomed, Albacete 13071, Spain

来源：

SCIENTIFIC REPORTS | 2020年 / 10卷 / 01期

关键词：

LOCALLY ADVANCED HEAD; EVOLUTIONARY ACTION SCORE; INDUCTION CHEMOTHERAPY; GENOMIC ALTERATIONS; RISK-FACTORS; CANCER; SURVIVAL; HPV; LANDSCAPE; IMMUNOHISTOCHEMISTRY;

D O I：

10.1038/s41598-020-72927-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p<0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p<0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours.

引用

页数：12

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