Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)

Abstract Carcinoma of Unknown Primary (CUP) is a heterogeneous and metastatic disease where the primary site of origin is undetectable. Currently, chemotherapy is the only state-of-art treatment option for CUP patients. The molecular profiling of the tumour, particularly mutation detection, offers a...

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Autores principales:	Hamidreza Aboulkheyr Es, Hamid Mahdizadeh, Amir Abbas Hedayati Asl, Mehdi Totonchi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f1fe39e7ef8448c2826eda7bf9a46cfb
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spelling	oai:doaj.org-article:f1fe39e7ef8448c2826eda7bf9a46cfb2021-12-02T16:50:25ZGenomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)10.1038/s41598-021-94678-42045-2322https://doaj.org/article/f1fe39e7ef8448c2826eda7bf9a46cfb2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94678-4https://doaj.org/toc/2045-2322Abstract Carcinoma of Unknown Primary (CUP) is a heterogeneous and metastatic disease where the primary site of origin is undetectable. Currently, chemotherapy is the only state-of-art treatment option for CUP patients. The molecular profiling of the tumour, particularly mutation detection, offers a new treatment approach for CUP in a personalized fashion using targeted agents. We analyzed the mutation and copy number alterations profile of 1709 CUP samples deposited in the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) cohort and explored potentially druggable mutations. We identified 52 significant mutated genes (SMGs) among CUP samples, in which 13 (25%) of SMGs were potentially targetable with either drugs are approved for the know primary tumour or undergoing clinical trials. The most variants detected were TP53 (43%), KRAS (19.90%), KMT2D (12.60%), and CDKN2A (10.30%). Additionally, using pan-cancer analysis, we found similar variants of TERT promoter in CUP and NSCLC samples, suggesting that these mutations may serve as a diagnostic marker for identifying the primary tumour in CUP. Taken together, the mutation profiling analysis of the CUP tumours may open a new way of identifying druggable targets and consequently administrating appropriate treatment in a personalized manner.Hamidreza Aboulkheyr EsHamid MahdizadehAmir Abbas Hedayati AslMehdi TotonchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hamidreza Aboulkheyr Es Hamid Mahdizadeh Amir Abbas Hedayati Asl Mehdi Totonchi Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)
description	Abstract Carcinoma of Unknown Primary (CUP) is a heterogeneous and metastatic disease where the primary site of origin is undetectable. Currently, chemotherapy is the only state-of-art treatment option for CUP patients. The molecular profiling of the tumour, particularly mutation detection, offers a new treatment approach for CUP in a personalized fashion using targeted agents. We analyzed the mutation and copy number alterations profile of 1709 CUP samples deposited in the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) cohort and explored potentially druggable mutations. We identified 52 significant mutated genes (SMGs) among CUP samples, in which 13 (25%) of SMGs were potentially targetable with either drugs are approved for the know primary tumour or undergoing clinical trials. The most variants detected were TP53 (43%), KRAS (19.90%), KMT2D (12.60%), and CDKN2A (10.30%). Additionally, using pan-cancer analysis, we found similar variants of TERT promoter in CUP and NSCLC samples, suggesting that these mutations may serve as a diagnostic marker for identifying the primary tumour in CUP. Taken together, the mutation profiling analysis of the CUP tumours may open a new way of identifying druggable targets and consequently administrating appropriate treatment in a personalized manner.
format	article
author	Hamidreza Aboulkheyr Es Hamid Mahdizadeh Amir Abbas Hedayati Asl Mehdi Totonchi
author_facet	Hamidreza Aboulkheyr Es Hamid Mahdizadeh Amir Abbas Hedayati Asl Mehdi Totonchi
author_sort	Hamidreza Aboulkheyr Es
title	Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)
title_short	Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)
title_full	Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)
title_fullStr	Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)
title_full_unstemmed	Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)
title_sort	genomic alterations and possible druggable mutations in carcinoma of unknown primary (cup)
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f1fe39e7ef8448c2826eda7bf9a46cfb
work_keys_str_mv	AT hamidrezaaboulkheyres genomicalterationsandpossibledruggablemutationsincarcinomaofunknownprimarycup AT hamidmahdizadeh genomicalterationsandpossibledruggablemutationsincarcinomaofunknownprimarycup AT amirabbashedayatiasl genomicalterationsandpossibledruggablemutationsincarcinomaofunknownprimarycup AT mehditotonchi genomicalterationsandpossibledruggablemutationsincarcinomaofunknownprimarycup
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Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)

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