Intragenic NF1 deletions in sinonasal mucosal malignant melanoma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F22%3A10439005" target="_blank" >RIV/00216208:11150/22:10439005 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/22:10439005

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=lZKvfBg7n7" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=lZKvfBg7n7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/pcmr.13015" target="_blank" >10.1111/pcmr.13015</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Intragenic NF1 deletions in sinonasal mucosal malignant melanoma

Popis výsledku v původním jazyce

Mucosal malignant melanoma (MMM) is a rare and aggressive tumor. Despite effective local therapies, tumor recurrence and metastasis remain frequent. The genetics of MMM remain incompletely understood. This study is aimed to identify actionable genetic alterations by next-generation sequencing. Fifteen MMM samples were analyzed by next-generation and Sanger sequencing. Gene copy number alterations were analyzed by MLPA. Mutation status was correlated with pERK, pAKT, and Ki-67 expression and follow-up data. Inactivating mutations and intragenic deletions in neurofibromatosis type-1 (NF1) were identified in 3 and 2 cases, respectively, (in total 5/15, 33%) and activating mutations in NRAS and KRAS (3/15, 20%) cases. Other mutated genes included CDKN2A, APC, ATM, MITF, FGFR1, and FGFR2. BRAF and KIT mutations were not observed. Cases with NF1 alterations tended to have worse overall survival. The mutational status was not associated with pERK, pAKT, or Ki-67 immunostaining. MMM carries frequent gene mutations activating the MAPK pathway, similar to cutaneous melanoma. In contrast, NF1 is the most frequently affected gene. Intragenic NF1 deletions have not been described before and may go undetected by sequencing studies. This finding is clinically relevant as NF1-mutated melanomas have worse survival and could benefit from therapy with immune checkpoint and MEK inhibitors.

Název v anglickém jazyce

Intragenic NF1 deletions in sinonasal mucosal malignant melanoma

Popis výsledku anglicky

Mucosal malignant melanoma (MMM) is a rare and aggressive tumor. Despite effective local therapies, tumor recurrence and metastasis remain frequent. The genetics of MMM remain incompletely understood. This study is aimed to identify actionable genetic alterations by next-generation sequencing. Fifteen MMM samples were analyzed by next-generation and Sanger sequencing. Gene copy number alterations were analyzed by MLPA. Mutation status was correlated with pERK, pAKT, and Ki-67 expression and follow-up data. Inactivating mutations and intragenic deletions in neurofibromatosis type-1 (NF1) were identified in 3 and 2 cases, respectively, (in total 5/15, 33%) and activating mutations in NRAS and KRAS (3/15, 20%) cases. Other mutated genes included CDKN2A, APC, ATM, MITF, FGFR1, and FGFR2. BRAF and KIT mutations were not observed. Cases with NF1 alterations tended to have worse overall survival. The mutational status was not associated with pERK, pAKT, or Ki-67 immunostaining. MMM carries frequent gene mutations activating the MAPK pathway, similar to cutaneous melanoma. In contrast, NF1 is the most frequently affected gene. Intragenic NF1 deletions have not been described before and may go undetected by sequencing studies. This finding is clinically relevant as NF1-mutated melanomas have worse survival and could benefit from therapy with immune checkpoint and MEK inhibitors.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Pigment Cell and Melanoma Research

ISSN

1755-1471

e-ISSN

1755-148X

Svazek periodika

35

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DK - Dánské království

Počet stran výsledku

9

Strana od-do

88-96

Kód UT WoS článku

000704536700001

EID výsledku v databázi Scopus

2-s2.0-85116434557