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Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture‐Based Assay of Circulating Tumor DNA

ALK rearrangements have been observed in 0.05%–2.5% of patients with colorectal cancers (CRCs) and are predicted to be oncogenic drivers largely mutually exclusive of KRAS, NRAS, or BRAF alterations. Here we present the case of a patient with metastatic CRC who was treatment naïve at the time of mol...

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Autores principales: Lai, Andrea Z., Schrock, Alexa B., Erlich, Rachel L., Ross, Jeffrey S., Miller, Vincent A., Yakirevich, Evgeny, Ali, Siraj M., Braiteh, Fadi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AlphaMed Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507649/
https://www.ncbi.nlm.nih.gov/pubmed/28507204
http://dx.doi.org/10.1634/theoncologist.2016-0376
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author Lai, Andrea Z.
Schrock, Alexa B.
Erlich, Rachel L.
Ross, Jeffrey S.
Miller, Vincent A.
Yakirevich, Evgeny
Ali, Siraj M.
Braiteh, Fadi
author_facet Lai, Andrea Z.
Schrock, Alexa B.
Erlich, Rachel L.
Ross, Jeffrey S.
Miller, Vincent A.
Yakirevich, Evgeny
Ali, Siraj M.
Braiteh, Fadi
author_sort Lai, Andrea Z.
collection PubMed
description ALK rearrangements have been observed in 0.05%–2.5% of patients with colorectal cancers (CRCs) and are predicted to be oncogenic drivers largely mutually exclusive of KRAS, NRAS, or BRAF alterations. Here we present the case of a patient with metastatic CRC who was treatment naïve at the time of molecular testing. Initial ALK immunohistochemistry (IHC) staining was negative, but parallel genomic profiling of both circulating tumor DNA (ctDNA) and tissue using similar hybrid capture‐based assays each identified an identical STRN‐ALK fusion. Subsequent ALK IHC staining of the same specimens was positive, suggesting that the initial result was a false negative. This report is the first instance of an ALK fusion in CRC detected using a ctDNA assay. KEY POINTS. Current guidelines for colorectal cancer (CRC) only recommend genomic assessment of KRAS, NRAS, BRAF, and microsatellite instability (MSI) status. ALK rearrangements are rare in CRC, but patients with activating ALK fusions have responded to targeted therapies. ALK rearrangements can be detected by genomic profiling of ctDNA from blood or tissue, and this methodology may be informative in cases where immunohistochemistry (IHC) or other standard testing is negative.
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spelling pubmed-55076492017-07-13 Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture‐Based Assay of Circulating Tumor DNA Lai, Andrea Z. Schrock, Alexa B. Erlich, Rachel L. Ross, Jeffrey S. Miller, Vincent A. Yakirevich, Evgeny Ali, Siraj M. Braiteh, Fadi Oncologist Precision Medicine Clinic ALK rearrangements have been observed in 0.05%–2.5% of patients with colorectal cancers (CRCs) and are predicted to be oncogenic drivers largely mutually exclusive of KRAS, NRAS, or BRAF alterations. Here we present the case of a patient with metastatic CRC who was treatment naïve at the time of molecular testing. Initial ALK immunohistochemistry (IHC) staining was negative, but parallel genomic profiling of both circulating tumor DNA (ctDNA) and tissue using similar hybrid capture‐based assays each identified an identical STRN‐ALK fusion. Subsequent ALK IHC staining of the same specimens was positive, suggesting that the initial result was a false negative. This report is the first instance of an ALK fusion in CRC detected using a ctDNA assay. KEY POINTS. Current guidelines for colorectal cancer (CRC) only recommend genomic assessment of KRAS, NRAS, BRAF, and microsatellite instability (MSI) status. ALK rearrangements are rare in CRC, but patients with activating ALK fusions have responded to targeted therapies. ALK rearrangements can be detected by genomic profiling of ctDNA from blood or tissue, and this methodology may be informative in cases where immunohistochemistry (IHC) or other standard testing is negative. AlphaMed Press 2017-05-15 2017-07 /pmc/articles/PMC5507649/ /pubmed/28507204 http://dx.doi.org/10.1634/theoncologist.2016-0376 Text en © AlphaMed Press 2017
spellingShingle Precision Medicine Clinic
Lai, Andrea Z.
Schrock, Alexa B.
Erlich, Rachel L.
Ross, Jeffrey S.
Miller, Vincent A.
Yakirevich, Evgeny
Ali, Siraj M.
Braiteh, Fadi
Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture‐Based Assay of Circulating Tumor DNA
title Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture‐Based Assay of Circulating Tumor DNA
title_full Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture‐Based Assay of Circulating Tumor DNA
title_fullStr Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture‐Based Assay of Circulating Tumor DNA
title_full_unstemmed Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture‐Based Assay of Circulating Tumor DNA
title_short Detection of an ALK Fusion in Colorectal Carcinoma by Hybrid Capture‐Based Assay of Circulating Tumor DNA
title_sort detection of an alk fusion in colorectal carcinoma by hybrid capture‐based assay of circulating tumor dna
topic Precision Medicine Clinic
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507649/
https://www.ncbi.nlm.nih.gov/pubmed/28507204
http://dx.doi.org/10.1634/theoncologist.2016-0376
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