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Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population
Anaplastic lymphoma kinase (ALK) rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients. Tissue microarray (TMA) was constructed...
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| Published in: | PloS one 2015-12, Vol.10 (12), p.e0144731-e0144731 |
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| container_end_page | e0144731 |
| container_issue | 12 |
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| creator | Ying, Jianming Lin, Chen Wu, Jian Guo, Lei Qiu, Tian Ling, Yun Shan, Ling Zhou, Haitao Zhao, Dongbing Wang, Jian Liang, Jianwei Zhao, Jianjun Jiao, Yuchen Lu, Ning Zhao, Hong |
| description | Anaplastic lymphoma kinase (ALK) rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.
Tissue microarray (TMA) was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC) cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC) assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (qRT-PCR), target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.
Among the tested cases, 2 (0.44%) CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1). One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.
The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy. |
| doi_str_mv | 10.1371/journal.pone.0144731 |
| format | article |
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Tissue microarray (TMA) was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC) cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC) assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (qRT-PCR), target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.
Among the tested cases, 2 (0.44%) CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1). One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.
The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0144731</identifier><identifier>PMID: 26678488</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abdomen ; Adult ; Aged ; ALK protein ; Analysis ; Asian Continental Ancestry Group - genetics ; Automation ; Biomarkers ; Cancer ; Cancer therapies ; Chemotherapy ; China ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - enzymology ; Colorectal Neoplasms - genetics ; Diagnosis ; Digestive tract ; DNA microarrays ; DNA, Neoplasm - genetics ; Enrichment ; Epidermal growth factor ; Esophageal Neoplasms - enzymology ; Esophageal Neoplasms - genetics ; Esophagus ; Female ; Fluorescence ; Fluorescence in situ hybridization ; Gastric cancer ; Gastrointestinal tract ; Gene fusion ; Gene Rearrangement ; Gene sequencing ; Genes ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Incidence ; Kinases ; Laboratories ; Lung cancer ; Lung diseases ; Lymphoma ; Lymphomas ; Male ; Medical diagnosis ; Membrane proteins ; Metastasis ; Middle Aged ; Neoplasms, Squamous Cell - enzymology ; Neoplasms, Squamous Cell - genetics ; Oncology ; Pathology ; Patients ; Physicians ; Physiological aspects ; Polymerase chain reaction ; Protein-tyrosine kinase ; Real-Time Polymerase Chain Reaction ; Receptor Protein-Tyrosine Kinases - genetics ; Spectrin ; Squamous cell carcinoma ; Stomach cancer ; Stomach Neoplasms - enzymology ; Stomach Neoplasms - genetics ; Targeted Gene Repair - methods ; Therapy ; Tissue Array Analysis ; Tumors ; Young Adult</subject><ispartof>PloS one, 2015-12, Vol.10 (12), p.e0144731-e0144731</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Ying et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Ying et al 2015 Ying et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-eb485a9bb652bf36b73b0e2018f162bf3db367388dc2c4059bb39030b9acf9993</citedby><cites>FETCH-LOGICAL-c758t-eb485a9bb652bf36b73b0e2018f162bf3db367388dc2c4059bb39030b9acf9993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1749962142/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1749962142?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26678488$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kumar-Sinha, Chandan</contributor><creatorcontrib>Ying, Jianming</creatorcontrib><creatorcontrib>Lin, Chen</creatorcontrib><creatorcontrib>Wu, Jian</creatorcontrib><creatorcontrib>Guo, Lei</creatorcontrib><creatorcontrib>Qiu, Tian</creatorcontrib><creatorcontrib>Ling, Yun</creatorcontrib><creatorcontrib>Shan, Ling</creatorcontrib><creatorcontrib>Zhou, Haitao</creatorcontrib><creatorcontrib>Zhao, Dongbing</creatorcontrib><creatorcontrib>Wang, Jian</creatorcontrib><creatorcontrib>Liang, Jianwei</creatorcontrib><creatorcontrib>Zhao, Jianjun</creatorcontrib><creatorcontrib>Jiao, Yuchen</creatorcontrib><creatorcontrib>Lu, Ning</creatorcontrib><creatorcontrib>Zhao, Hong</creatorcontrib><title>Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Anaplastic lymphoma kinase (ALK) rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.
Tissue microarray (TMA) was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC) cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC) assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (qRT-PCR), target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.
Among the tested cases, 2 (0.44%) CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1). One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.
The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.</description><subject>Abdomen</subject><subject>Adult</subject><subject>Aged</subject><subject>ALK protein</subject><subject>Analysis</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Automation</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>China</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - enzymology</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Diagnosis</subject><subject>Digestive tract</subject><subject>DNA microarrays</subject><subject>DNA, Neoplasm - genetics</subject><subject>Enrichment</subject><subject>Epidermal growth factor</subject><subject>Esophageal Neoplasms - enzymology</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophagus</subject><subject>Female</subject><subject>Fluorescence</subject><subject>Fluorescence in situ hybridization</subject><subject>Gastric cancer</subject><subject>Gastrointestinal tract</subject><subject>Gene fusion</subject><subject>Gene Rearrangement</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Incidence</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Lymphoma</subject><subject>Lymphomas</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Membrane proteins</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Neoplasms, Squamous Cell - enzymology</subject><subject>Neoplasms, Squamous Cell - genetics</subject><subject>Oncology</subject><subject>Pathology</subject><subject>Patients</subject><subject>Physicians</subject><subject>Physiological aspects</subject><subject>Polymerase chain reaction</subject><subject>Protein-tyrosine kinase</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Spectrin</subject><subject>Squamous cell carcinoma</subject><subject>Stomach cancer</subject><subject>Stomach Neoplasms - enzymology</subject><subject>Stomach Neoplasms - genetics</subject><subject>Targeted Gene Repair - methods</subject><subject>Therapy</subject><subject>Tissue Array Analysis</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk19v0zAUxSMEYqPwDRBEQkLw0OLEjhPvAakq_yoqDY3Cq3Xj2KmrxA52MlE-Pc7aTS3aA8pDopvfOdc-9o2i5wmaJThP3m3t4Aw0s84aOUMJITlOHkTnCcPplKYIPzz6PoueeL9FKMMFpY-js5TSvCBFcR79mRvoGvC9FvFq13Yb20L8VRvwMr6S4ByYWrbS9LE28Qddy0Bey3jtQPTxAoyQ7iJetl2jBfTamlhZF6_B1bKXVbzeSAfdbtQuNtrIYPrNdkNzgz6NHilovHx2eE-iH58-rhdfpqvLz8vFfDUVeVb0U1mSIgNWljRLS4VpmeMSyRQlhUroWKlKTHNcFJVIBUFZIDFDGJUMhGKM4Un0cu_bNdbzQ2yeJzlhjKYJSQOx3BOVhS3vnG7B7bgFzW8K1tUcXEiokZxQVhVIKJnRglShm2AVE1QBVkxhpYLX-0O3oWxlJUJ0DpoT09M_Rm94ba-Dc4FRToPBm4OBs7-GkDdvtReyacBIO4zrzhDBGQvHOole_YPev7sDVUPYgDbKhr5iNOVzgvM8y0ieBGp2DxWeSrZahDumdKifCN6eCALTy999DYP3fPn96v_Zy5-n7OsjdiOh6TfeNsN4ZfwpSPagcNZ7J9VdyAni44jcpsHHEeGHEQmyF8cHdCe6nQn8F3KFDRc</recordid><startdate>20151217</startdate><enddate>20151217</enddate><creator>Ying, Jianming</creator><creator>Lin, Chen</creator><creator>Wu, Jian</creator><creator>Guo, Lei</creator><creator>Qiu, Tian</creator><creator>Ling, Yun</creator><creator>Shan, Ling</creator><creator>Zhou, Haitao</creator><creator>Zhao, Dongbing</creator><creator>Wang, Jian</creator><creator>Liang, Jianwei</creator><creator>Zhao, Jianjun</creator><creator>Jiao, Yuchen</creator><creator>Lu, Ning</creator><creator>Zhao, Hong</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20151217</creationdate><title>Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population</title><author>Ying, Jianming ; Lin, Chen ; Wu, Jian ; Guo, Lei ; Qiu, Tian ; Ling, Yun ; Shan, Ling ; Zhou, Haitao ; Zhao, Dongbing ; Wang, Jian ; Liang, Jianwei ; Zhao, Jianjun ; Jiao, Yuchen ; Lu, Ning ; Zhao, Hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-eb485a9bb652bf36b73b0e2018f162bf3db367388dc2c4059bb39030b9acf9993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Abdomen</topic><topic>Adult</topic><topic>Aged</topic><topic>ALK protein</topic><topic>Analysis</topic><topic>Asian Continental Ancestry Group - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ying, Jianming</au><au>Lin, Chen</au><au>Wu, Jian</au><au>Guo, Lei</au><au>Qiu, Tian</au><au>Ling, Yun</au><au>Shan, Ling</au><au>Zhou, Haitao</au><au>Zhao, Dongbing</au><au>Wang, Jian</au><au>Liang, Jianwei</au><au>Zhao, Jianjun</au><au>Jiao, Yuchen</au><au>Lu, Ning</au><au>Zhao, Hong</au><au>Kumar-Sinha, Chandan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-12-17</date><risdate>2015</risdate><volume>10</volume><issue>12</issue><spage>e0144731</spage><epage>e0144731</epage><pages>e0144731-e0144731</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Anaplastic lymphoma kinase (ALK) rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.
Tissue microarray (TMA) was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC) cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC) assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (qRT-PCR), target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.
Among the tested cases, 2 (0.44%) CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1). One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.
The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26678488</pmid><doi>10.1371/journal.pone.0144731</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-12, Vol.10 (12), p.e0144731-e0144731 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1749962142 |
| source | PubMed Central(OpenAccess); ProQuest - Publicly Available Content Database |
| subjects | Abdomen Adult Aged ALK protein Analysis Asian Continental Ancestry Group - genetics Automation Biomarkers Cancer Cancer therapies Chemotherapy China Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - enzymology Colorectal Neoplasms - genetics Diagnosis Digestive tract DNA microarrays DNA, Neoplasm - genetics Enrichment Epidermal growth factor Esophageal Neoplasms - enzymology Esophageal Neoplasms - genetics Esophagus Female Fluorescence Fluorescence in situ hybridization Gastric cancer Gastrointestinal tract Gene fusion Gene Rearrangement Gene sequencing Genes Humans Immunohistochemistry In Situ Hybridization, Fluorescence Incidence Kinases Laboratories Lung cancer Lung diseases Lymphoma Lymphomas Male Medical diagnosis Membrane proteins Metastasis Middle Aged Neoplasms, Squamous Cell - enzymology Neoplasms, Squamous Cell - genetics Oncology Pathology Patients Physicians Physiological aspects Polymerase chain reaction Protein-tyrosine kinase Real-Time Polymerase Chain Reaction Receptor Protein-Tyrosine Kinases - genetics Spectrin Squamous cell carcinoma Stomach cancer Stomach Neoplasms - enzymology Stomach Neoplasms - genetics Targeted Gene Repair - methods Therapy Tissue Array Analysis Tumors Young Adult |
| title | Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population |
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