Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms
Mutations in JAK2 , MPL and CALR genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients...
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| Veröffentlicht in: | Medical oncology (Northwood, London, England) London, England), 2017-05, Vol.34 (5), p.83-83, Article 83 |
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| creator | Chang, Yu-Cheng Lin, Huan-Chau Chiang, Yi-Hao Chen, Caleb Gon-Shen Huang, Ling Wang, Wei-Ting Cheng, Chun-Chia Lin, Johnson Chang, Yi-Fang Chang, Ming-Chih Hsieh, Ruey-Kuen Chen, Shu-Jen Lim, Ken-Hong Kuo, Yuan-Yeh |
| description | Mutations in
JAK2
,
MPL
and
CALR
genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients including 7 essential thrombocythemia (ET), 1 primary myelofibrosis and 8 polycythemia vera (PV). Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes. Overall, 30 nonsynonymous somatic mutations were detected in 12 (75%) patients with a range of 1–5 mutations per sample. Notably, one ET patient was found to have
JAK2
V617F and
KIT
P551L mutations at very low allele frequency. One
MPL
P70L and 1
MPL
M602T mutations were identified each in 1 ET and 1 PV, respectively. Other recurrent mutations were also identified including
KMT2C
,
KMT2D
,
IRS2
,
SYNE1
,
PDE4DIP
,
SETD2
,
ATM
,
TNFAIP3
and
CCND2
. In addition, germline mutations were also found in some cancer-related genes. Copy number changes were rare in this cohort of TN MPNs. In conclusion, both somatic and germline mutations can be detected in TN MPN patients. |
| doi_str_mv | 10.1007/s12032-017-0944-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1885950796</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1885950796</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-d152723f6d0ed4d95be11e393a77a72c4e5e238fabcec17a3c605133f48440f73</originalsourceid><addsrcrecordid>eNp1kUtLxDAUhYMozvj4AW6k4MZNNI-maZYy-ALBzQjuQqa9LRnadEzawZlfb-ahiOAq4d7vnnuSg9AFJTeUEHkbKCOcYUIlJipN8foAjakQClNO3w_jnYvYERkZoZMQ5oQwKpg6RiOW81wpIsfITY2voYcycfDZ4xoceNPbziUBPgZwhXV1Yktwva3shuqW0CTt0G-hkFiX9N4uGsAO6lhbQtKuoOkWvmtstdWKJQfdojGhDWfoqDJNgPP9eYreHu6nkyf88vr4PLl7wQWXrMdl9CkZr7KSQJmWSsyAUuCKGymNZEUKAhjPKzMroKDS8CIjgnJepXmakkryU3S9040-4jNCr1sbCmgaE60MQdM8F0oQqbKIXv1B593gXXS3pahiWcYiRXdU4bsQPFR64W1r_EpTojdh6F0YOoahN2HodZy53CsPsxbKn4nv348A2wEhtlwN_tfqf1W_AFJGl8g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1885192662</pqid></control><display><type>article</type><title>Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Chang, Yu-Cheng ; Lin, Huan-Chau ; Chiang, Yi-Hao ; Chen, Caleb Gon-Shen ; Huang, Ling ; Wang, Wei-Ting ; Cheng, Chun-Chia ; Lin, Johnson ; Chang, Yi-Fang ; Chang, Ming-Chih ; Hsieh, Ruey-Kuen ; Chen, Shu-Jen ; Lim, Ken-Hong ; Kuo, Yuan-Yeh</creator><creatorcontrib>Chang, Yu-Cheng ; Lin, Huan-Chau ; Chiang, Yi-Hao ; Chen, Caleb Gon-Shen ; Huang, Ling ; Wang, Wei-Ting ; Cheng, Chun-Chia ; Lin, Johnson ; Chang, Yi-Fang ; Chang, Ming-Chih ; Hsieh, Ruey-Kuen ; Chen, Shu-Jen ; Lim, Ken-Hong ; Kuo, Yuan-Yeh</creatorcontrib><description>Mutations in
JAK2
,
MPL
and
CALR
genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients including 7 essential thrombocythemia (ET), 1 primary myelofibrosis and 8 polycythemia vera (PV). Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes. Overall, 30 nonsynonymous somatic mutations were detected in 12 (75%) patients with a range of 1–5 mutations per sample. Notably, one ET patient was found to have
JAK2
V617F and
KIT
P551L mutations at very low allele frequency. One
MPL
P70L and 1
MPL
M602T mutations were identified each in 1 ET and 1 PV, respectively. Other recurrent mutations were also identified including
KMT2C
,
KMT2D
,
IRS2
,
SYNE1
,
PDE4DIP
,
SETD2
,
ATM
,
TNFAIP3
and
CCND2
. In addition, germline mutations were also found in some cancer-related genes. Copy number changes were rare in this cohort of TN MPNs. In conclusion, both somatic and germline mutations can be detected in TN MPN patients.</description><identifier>ISSN: 1357-0560</identifier><identifier>EISSN: 1559-131X</identifier><identifier>DOI: 10.1007/s12032-017-0944-z</identifier><identifier>PMID: 28389907</identifier><identifier>CODEN: MONCEZ</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Calreticulin - genetics ; DNA Mutational Analysis - methods ; DNA, Neoplasm - blood ; DNA, Neoplasm - genetics ; Female ; Germ-Line Mutation ; Hematology ; Humans ; Internal Medicine ; Janus Kinase 2 - genetics ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Mutation ; Myeloproliferative Disorders - blood ; Myeloproliferative Disorders - genetics ; Oncology ; Original Paper ; Pathology ; Receptors, Thrombopoietin - genetics ; Sequence Analysis, DNA - methods</subject><ispartof>Medical oncology (Northwood, London, England), 2017-05, Vol.34 (5), p.83-83, Article 83</ispartof><rights>Springer Science+Business Media New York 2017</rights><rights>Medical Oncology is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-d152723f6d0ed4d95be11e393a77a72c4e5e238fabcec17a3c605133f48440f73</citedby><cites>FETCH-LOGICAL-c372t-d152723f6d0ed4d95be11e393a77a72c4e5e238fabcec17a3c605133f48440f73</cites><orcidid>0000-0003-2282-0416</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12032-017-0944-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12032-017-0944-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28389907$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Yu-Cheng</creatorcontrib><creatorcontrib>Lin, Huan-Chau</creatorcontrib><creatorcontrib>Chiang, Yi-Hao</creatorcontrib><creatorcontrib>Chen, Caleb Gon-Shen</creatorcontrib><creatorcontrib>Huang, Ling</creatorcontrib><creatorcontrib>Wang, Wei-Ting</creatorcontrib><creatorcontrib>Cheng, Chun-Chia</creatorcontrib><creatorcontrib>Lin, Johnson</creatorcontrib><creatorcontrib>Chang, Yi-Fang</creatorcontrib><creatorcontrib>Chang, Ming-Chih</creatorcontrib><creatorcontrib>Hsieh, Ruey-Kuen</creatorcontrib><creatorcontrib>Chen, Shu-Jen</creatorcontrib><creatorcontrib>Lim, Ken-Hong</creatorcontrib><creatorcontrib>Kuo, Yuan-Yeh</creatorcontrib><title>Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms</title><title>Medical oncology (Northwood, London, England)</title><addtitle>Med Oncol</addtitle><addtitle>Med Oncol</addtitle><description>Mutations in
JAK2
,
MPL
and
CALR
genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients including 7 essential thrombocythemia (ET), 1 primary myelofibrosis and 8 polycythemia vera (PV). Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes. Overall, 30 nonsynonymous somatic mutations were detected in 12 (75%) patients with a range of 1–5 mutations per sample. Notably, one ET patient was found to have
JAK2
V617F and
KIT
P551L mutations at very low allele frequency. One
MPL
P70L and 1
MPL
M602T mutations were identified each in 1 ET and 1 PV, respectively. Other recurrent mutations were also identified including
KMT2C
,
KMT2D
,
IRS2
,
SYNE1
,
PDE4DIP
,
SETD2
,
ATM
,
TNFAIP3
and
CCND2
. In addition, germline mutations were also found in some cancer-related genes. Copy number changes were rare in this cohort of TN MPNs. In conclusion, both somatic and germline mutations can be detected in TN MPN patients.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Calreticulin - genetics</subject><subject>DNA Mutational Analysis - methods</subject><subject>DNA, Neoplasm - blood</subject><subject>DNA, Neoplasm - genetics</subject><subject>Female</subject><subject>Germ-Line Mutation</subject><subject>Hematology</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Janus Kinase 2 - genetics</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Myeloproliferative Disorders - blood</subject><subject>Myeloproliferative Disorders - genetics</subject><subject>Oncology</subject><subject>Original Paper</subject><subject>Pathology</subject><subject>Receptors, Thrombopoietin - genetics</subject><subject>Sequence Analysis, DNA - methods</subject><issn>1357-0560</issn><issn>1559-131X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUtLxDAUhYMozvj4AW6k4MZNNI-maZYy-ALBzQjuQqa9LRnadEzawZlfb-ahiOAq4d7vnnuSg9AFJTeUEHkbKCOcYUIlJipN8foAjakQClNO3w_jnYvYERkZoZMQ5oQwKpg6RiOW81wpIsfITY2voYcycfDZ4xoceNPbziUBPgZwhXV1Yktwva3shuqW0CTt0G-hkFiX9N4uGsAO6lhbQtKuoOkWvmtstdWKJQfdojGhDWfoqDJNgPP9eYreHu6nkyf88vr4PLl7wQWXrMdl9CkZr7KSQJmWSsyAUuCKGymNZEUKAhjPKzMroKDS8CIjgnJepXmakkryU3S9040-4jNCr1sbCmgaE60MQdM8F0oQqbKIXv1B593gXXS3pahiWcYiRXdU4bsQPFR64W1r_EpTojdh6F0YOoahN2HodZy53CsPsxbKn4nv348A2wEhtlwN_tfqf1W_AFJGl8g</recordid><startdate>20170501</startdate><enddate>20170501</enddate><creator>Chang, Yu-Cheng</creator><creator>Lin, Huan-Chau</creator><creator>Chiang, Yi-Hao</creator><creator>Chen, Caleb Gon-Shen</creator><creator>Huang, Ling</creator><creator>Wang, Wei-Ting</creator><creator>Cheng, Chun-Chia</creator><creator>Lin, Johnson</creator><creator>Chang, Yi-Fang</creator><creator>Chang, Ming-Chih</creator><creator>Hsieh, Ruey-Kuen</creator><creator>Chen, Shu-Jen</creator><creator>Lim, Ken-Hong</creator><creator>Kuo, Yuan-Yeh</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2282-0416</orcidid></search><sort><creationdate>20170501</creationdate><title>Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms</title><author>Chang, Yu-Cheng ; Lin, Huan-Chau ; Chiang, Yi-Hao ; Chen, Caleb Gon-Shen ; Huang, Ling ; Wang, Wei-Ting ; Cheng, Chun-Chia ; Lin, Johnson ; Chang, Yi-Fang ; Chang, Ming-Chih ; Hsieh, Ruey-Kuen ; Chen, Shu-Jen ; Lim, Ken-Hong ; Kuo, Yuan-Yeh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-d152723f6d0ed4d95be11e393a77a72c4e5e238fabcec17a3c605133f48440f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Calreticulin - genetics</topic><topic>DNA Mutational Analysis - methods</topic><topic>DNA, Neoplasm - blood</topic><topic>DNA, Neoplasm - genetics</topic><topic>Female</topic><topic>Germ-Line Mutation</topic><topic>Hematology</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Janus Kinase 2 - genetics</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Myeloproliferative Disorders - blood</topic><topic>Myeloproliferative Disorders - genetics</topic><topic>Oncology</topic><topic>Original Paper</topic><topic>Pathology</topic><topic>Receptors, Thrombopoietin - genetics</topic><topic>Sequence Analysis, DNA - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Yu-Cheng</creatorcontrib><creatorcontrib>Lin, Huan-Chau</creatorcontrib><creatorcontrib>Chiang, Yi-Hao</creatorcontrib><creatorcontrib>Chen, Caleb Gon-Shen</creatorcontrib><creatorcontrib>Huang, Ling</creatorcontrib><creatorcontrib>Wang, Wei-Ting</creatorcontrib><creatorcontrib>Cheng, Chun-Chia</creatorcontrib><creatorcontrib>Lin, Johnson</creatorcontrib><creatorcontrib>Chang, Yi-Fang</creatorcontrib><creatorcontrib>Chang, Ming-Chih</creatorcontrib><creatorcontrib>Hsieh, Ruey-Kuen</creatorcontrib><creatorcontrib>Chen, Shu-Jen</creatorcontrib><creatorcontrib>Lim, Ken-Hong</creatorcontrib><creatorcontrib>Kuo, Yuan-Yeh</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Medical oncology (Northwood, London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Yu-Cheng</au><au>Lin, Huan-Chau</au><au>Chiang, Yi-Hao</au><au>Chen, Caleb Gon-Shen</au><au>Huang, Ling</au><au>Wang, Wei-Ting</au><au>Cheng, Chun-Chia</au><au>Lin, Johnson</au><au>Chang, Yi-Fang</au><au>Chang, Ming-Chih</au><au>Hsieh, Ruey-Kuen</au><au>Chen, Shu-Jen</au><au>Lim, Ken-Hong</au><au>Kuo, Yuan-Yeh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms</atitle><jtitle>Medical oncology (Northwood, London, England)</jtitle><stitle>Med Oncol</stitle><addtitle>Med Oncol</addtitle><date>2017-05-01</date><risdate>2017</risdate><volume>34</volume><issue>5</issue><spage>83</spage><epage>83</epage><pages>83-83</pages><artnum>83</artnum><issn>1357-0560</issn><eissn>1559-131X</eissn><coden>MONCEZ</coden><abstract>Mutations in
JAK2
,
MPL
and
CALR
genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients including 7 essential thrombocythemia (ET), 1 primary myelofibrosis and 8 polycythemia vera (PV). Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes. Overall, 30 nonsynonymous somatic mutations were detected in 12 (75%) patients with a range of 1–5 mutations per sample. Notably, one ET patient was found to have
JAK2
V617F and
KIT
P551L mutations at very low allele frequency. One
MPL
P70L and 1
MPL
M602T mutations were identified each in 1 ET and 1 PV, respectively. Other recurrent mutations were also identified including
KMT2C
,
KMT2D
,
IRS2
,
SYNE1
,
PDE4DIP
,
SETD2
,
ATM
,
TNFAIP3
and
CCND2
. In addition, germline mutations were also found in some cancer-related genes. Copy number changes were rare in this cohort of TN MPNs. In conclusion, both somatic and germline mutations can be detected in TN MPN patients.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28389907</pmid><doi>10.1007/s12032-017-0944-z</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-2282-0416</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1357-0560 |
| ispartof | Medical oncology (Northwood, London, England), 2017-05, Vol.34 (5), p.83-83, Article 83 |
| issn | 1357-0560 1559-131X |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Adolescent Adult Aged Aged, 80 and over Calreticulin - genetics DNA Mutational Analysis - methods DNA, Neoplasm - blood DNA, Neoplasm - genetics Female Germ-Line Mutation Hematology Humans Internal Medicine Janus Kinase 2 - genetics Male Medicine Medicine & Public Health Middle Aged Mutation Myeloproliferative Disorders - blood Myeloproliferative Disorders - genetics Oncology Original Paper Pathology Receptors, Thrombopoietin - genetics Sequence Analysis, DNA - methods |
| title | Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms |
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