Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients
Cervical cancer is the fourth most common cause of cancer-related deaths in Asian women, due to its poor prognosis. This study aimed to decipher genomic alteration profiles of a cohort of Japanese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies...
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| Veröffentlicht in: | Gynecologic oncology 2020-01, Vol.156 (1), p.203-210 |
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| creator | Hirose, Sou Murakami, Naoya Takahashi, Kazuaki Kuno, Ikumi Takayanagi, Daisuke Asami, Yuka Matsuda, Maiko Shimada, Yoko Yamano, Shotaro Sunami, Kuniko Yoshida, Kazushi Honda, Takayuki Nakahara, Tomomi Watanabe, Tomoko Komatsu, Masaaki Hamamoto, Ryuji Kato, Mayumi Kobayashi Matsumoto, Koji Okuma, Kae Kuroda, Takafumi Okamoto, Aikou Itami, Jun Kohno, Takashi Kato, Tomoyasu Shiraishi, Kouya Yoshida, Hiroshi |
| description | Cervical cancer is the fourth most common cause of cancer-related deaths in Asian women, due to its poor prognosis. This study aimed to decipher genomic alteration profiles of a cohort of Japanese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and their prognostic significance.
During 2008–2018, 154 cervical cancer patients underwent a potentially curative resection procedure at the National Cancer Center Hospital. Genomic DNA samples were analyzed using Ion AmpliSeq™ Cancer Hotspot Panel v2. Alterations in the copy number of PIK3CA, ERBB2, PTEN, and STK11 were detected using the TaqMan assay. HPV-positive results were confirmed by genomic testing and in situ hybridization assay.
The frequency of genomic alterations in PIK3CA (36%), STK11 (16%), PTEN (11%), TP53 (11%), and KRAS (8%) was >5%. KRAS mutations were preferentially detected in patients with adenocarcinomas, and the frequency of PIK3CA mutations in patients with squamous cell carcinomas was higher than that in patients with other histological cancer types. HPV-positive results were observed in 139/154 (90.3%) patients, and TP53 mutants were detected in HPV-negative specimens. In this study, the overall survival of patients with genomic alterations in STK11 was worse than in patients with wild–type STK11 (hazard ratio = 10.6, P = 0.0079) and TCGA dataset (hazard ratio = 2.46, P = 0.029).
More than one-third of Japanese cervical cancer patients exhibit mutations targeted by molecular targeted therapies. We have proposed the prognostic value of STK11 genomic alterations.
•Specific genomic alteration profiles were observed in cervical cancer (CC) patients.•These were correlated with certain histological types and HPV genotypes.•We detected actionable genomic alterations in 54 (35%) cervical cancer patients.•STK11 genomic alterations caused a worse prognosis in cervical cancer patients. |
| doi_str_mv | 10.1016/j.ygyno.2019.10.022 |
| format | Article |
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During 2008–2018, 154 cervical cancer patients underwent a potentially curative resection procedure at the National Cancer Center Hospital. Genomic DNA samples were analyzed using Ion AmpliSeq™ Cancer Hotspot Panel v2. Alterations in the copy number of PIK3CA, ERBB2, PTEN, and STK11 were detected using the TaqMan assay. HPV-positive results were confirmed by genomic testing and in situ hybridization assay.
The frequency of genomic alterations in PIK3CA (36%), STK11 (16%), PTEN (11%), TP53 (11%), and KRAS (8%) was >5%. KRAS mutations were preferentially detected in patients with adenocarcinomas, and the frequency of PIK3CA mutations in patients with squamous cell carcinomas was higher than that in patients with other histological cancer types. HPV-positive results were observed in 139/154 (90.3%) patients, and TP53 mutants were detected in HPV-negative specimens. In this study, the overall survival of patients with genomic alterations in STK11 was worse than in patients with wild–type STK11 (hazard ratio = 10.6, P = 0.0079) and TCGA dataset (hazard ratio = 2.46, P = 0.029).
More than one-third of Japanese cervical cancer patients exhibit mutations targeted by molecular targeted therapies. We have proposed the prognostic value of STK11 genomic alterations.
•Specific genomic alteration profiles were observed in cervical cancer (CC) patients.•These were correlated with certain histological types and HPV genotypes.•We detected actionable genomic alterations in 54 (35%) cervical cancer patients.•STK11 genomic alterations caused a worse prognosis in cervical cancer patients.</description><identifier>ISSN: 0090-8258</identifier><identifier>EISSN: 1095-6859</identifier><identifier>DOI: 10.1016/j.ygyno.2019.10.022</identifier><identifier>PMID: 31757465</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Asian Continental Ancestry Group - genetics ; Cervical cancer ; Clinical outcomes ; DNA Mutational Analysis ; DNA, Neoplasm - genetics ; DNA, Neoplasm - isolation & purification ; Female ; Humans ; Middle Aged ; Papillomaviridae - genetics ; Papillomavirus Infections - enzymology ; Papillomavirus Infections - genetics ; Papillomavirus Infections - pathology ; Papillomavirus Infections - virology ; Predictive Value of Tests ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; STK11 genomic alterations ; Uterine Cervical Neoplasms - enzymology ; Uterine Cervical Neoplasms - genetics ; Uterine Cervical Neoplasms - pathology ; Uterine Cervical Neoplasms - virology</subject><ispartof>Gynecologic oncology, 2020-01, Vol.156 (1), p.203-210</ispartof><rights>2019 Elsevier Inc.</rights><rights>Copyright © 2019 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-763c19dc7ba8c1d9b9cb145ba14e0a30cb9261c0e23f2f0027d83aea11aac1c93</citedby><cites>FETCH-LOGICAL-c425t-763c19dc7ba8c1d9b9cb145ba14e0a30cb9261c0e23f2f0027d83aea11aac1c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0090825819316063$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31757465$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hirose, Sou</creatorcontrib><creatorcontrib>Murakami, Naoya</creatorcontrib><creatorcontrib>Takahashi, Kazuaki</creatorcontrib><creatorcontrib>Kuno, Ikumi</creatorcontrib><creatorcontrib>Takayanagi, Daisuke</creatorcontrib><creatorcontrib>Asami, Yuka</creatorcontrib><creatorcontrib>Matsuda, Maiko</creatorcontrib><creatorcontrib>Shimada, Yoko</creatorcontrib><creatorcontrib>Yamano, Shotaro</creatorcontrib><creatorcontrib>Sunami, Kuniko</creatorcontrib><creatorcontrib>Yoshida, Kazushi</creatorcontrib><creatorcontrib>Honda, Takayuki</creatorcontrib><creatorcontrib>Nakahara, Tomomi</creatorcontrib><creatorcontrib>Watanabe, Tomoko</creatorcontrib><creatorcontrib>Komatsu, Masaaki</creatorcontrib><creatorcontrib>Hamamoto, Ryuji</creatorcontrib><creatorcontrib>Kato, Mayumi Kobayashi</creatorcontrib><creatorcontrib>Matsumoto, Koji</creatorcontrib><creatorcontrib>Okuma, Kae</creatorcontrib><creatorcontrib>Kuroda, Takafumi</creatorcontrib><creatorcontrib>Okamoto, Aikou</creatorcontrib><creatorcontrib>Itami, Jun</creatorcontrib><creatorcontrib>Kohno, Takashi</creatorcontrib><creatorcontrib>Kato, Tomoyasu</creatorcontrib><creatorcontrib>Shiraishi, Kouya</creatorcontrib><creatorcontrib>Yoshida, Hiroshi</creatorcontrib><title>Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients</title><title>Gynecologic oncology</title><addtitle>Gynecol Oncol</addtitle><description>Cervical cancer is the fourth most common cause of cancer-related deaths in Asian women, due to its poor prognosis. This study aimed to decipher genomic alteration profiles of a cohort of Japanese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and their prognostic significance.
During 2008–2018, 154 cervical cancer patients underwent a potentially curative resection procedure at the National Cancer Center Hospital. Genomic DNA samples were analyzed using Ion AmpliSeq™ Cancer Hotspot Panel v2. Alterations in the copy number of PIK3CA, ERBB2, PTEN, and STK11 were detected using the TaqMan assay. HPV-positive results were confirmed by genomic testing and in situ hybridization assay.
The frequency of genomic alterations in PIK3CA (36%), STK11 (16%), PTEN (11%), TP53 (11%), and KRAS (8%) was >5%. KRAS mutations were preferentially detected in patients with adenocarcinomas, and the frequency of PIK3CA mutations in patients with squamous cell carcinomas was higher than that in patients with other histological cancer types. HPV-positive results were observed in 139/154 (90.3%) patients, and TP53 mutants were detected in HPV-negative specimens. In this study, the overall survival of patients with genomic alterations in STK11 was worse than in patients with wild–type STK11 (hazard ratio = 10.6, P = 0.0079) and TCGA dataset (hazard ratio = 2.46, P = 0.029).
More than one-third of Japanese cervical cancer patients exhibit mutations targeted by molecular targeted therapies. We have proposed the prognostic value of STK11 genomic alterations.
•Specific genomic alteration profiles were observed in cervical cancer (CC) patients.•These were correlated with certain histological types and HPV genotypes.•We detected actionable genomic alterations in 54 (35%) cervical cancer patients.•STK11 genomic alterations caused a worse prognosis in cervical cancer patients.</description><subject>Asian Continental Ancestry Group - genetics</subject><subject>Cervical cancer</subject><subject>Clinical outcomes</subject><subject>DNA Mutational Analysis</subject><subject>DNA, Neoplasm - genetics</subject><subject>DNA, Neoplasm - isolation & purification</subject><subject>Female</subject><subject>Humans</subject><subject>Middle Aged</subject><subject>Papillomaviridae - genetics</subject><subject>Papillomavirus Infections - enzymology</subject><subject>Papillomavirus Infections - genetics</subject><subject>Papillomavirus Infections - pathology</subject><subject>Papillomavirus Infections - virology</subject><subject>Predictive Value of Tests</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>STK11 genomic alterations</subject><subject>Uterine Cervical Neoplasms - enzymology</subject><subject>Uterine Cervical Neoplasms - genetics</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Uterine Cervical Neoplasms - virology</subject><issn>0090-8258</issn><issn>1095-6859</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1PIzEMhqMVaCnd_QVIaI5cpthJ5yMHDgixLAKJA2WvUcbjrlLNTEoyReq_J22BIydbrx7b8iPEGcIMAcvL1Wz7fzv4mQTUKZmBlD_EBEEXeVkX-khMADTktSzqE3Ea4woAFKD8KU4UVkU1L4uJ-HfHg-8dZbYbOdjR-SFmbsieFw-IGdkhWwduHY0ZdW5wZLvMb0byPe8x4vC2DxOZ-mydNvAwxl_ieGm7yL8_6lS8_Lld3PzNH5_u7m-uH3Oay2LMq1IR6paqxtaErW40NTgvGotzBquAGi1LJGCplnIJIKu2VpYtorWEpNVUXBz2roN_3XAcTe8icdfZgf0mGrn7VCtZ1glVB5SCjzHw0qyD623YGgSzE2pWZi_U7ITuwiQ0TZ1_HNg0PbdfM58GE3B1ADi9-eY4mEhJASVpgWk0rXffHngHI-GIpw</recordid><startdate>202001</startdate><enddate>202001</enddate><creator>Hirose, Sou</creator><creator>Murakami, Naoya</creator><creator>Takahashi, Kazuaki</creator><creator>Kuno, Ikumi</creator><creator>Takayanagi, Daisuke</creator><creator>Asami, Yuka</creator><creator>Matsuda, Maiko</creator><creator>Shimada, Yoko</creator><creator>Yamano, Shotaro</creator><creator>Sunami, Kuniko</creator><creator>Yoshida, Kazushi</creator><creator>Honda, Takayuki</creator><creator>Nakahara, Tomomi</creator><creator>Watanabe, Tomoko</creator><creator>Komatsu, Masaaki</creator><creator>Hamamoto, Ryuji</creator><creator>Kato, Mayumi Kobayashi</creator><creator>Matsumoto, Koji</creator><creator>Okuma, Kae</creator><creator>Kuroda, Takafumi</creator><creator>Okamoto, Aikou</creator><creator>Itami, Jun</creator><creator>Kohno, Takashi</creator><creator>Kato, Tomoyasu</creator><creator>Shiraishi, Kouya</creator><creator>Yoshida, Hiroshi</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>202001</creationdate><title>Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients</title><author>Hirose, Sou ; Murakami, Naoya ; Takahashi, Kazuaki ; Kuno, Ikumi ; Takayanagi, Daisuke ; Asami, Yuka ; Matsuda, Maiko ; Shimada, Yoko ; Yamano, Shotaro ; Sunami, Kuniko ; Yoshida, Kazushi ; Honda, Takayuki ; Nakahara, Tomomi ; Watanabe, Tomoko ; Komatsu, Masaaki ; Hamamoto, Ryuji ; Kato, Mayumi Kobayashi ; Matsumoto, Koji ; Okuma, Kae ; Kuroda, Takafumi ; Okamoto, Aikou ; Itami, Jun ; Kohno, Takashi ; Kato, Tomoyasu ; Shiraishi, Kouya ; Yoshida, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c425t-763c19dc7ba8c1d9b9cb145ba14e0a30cb9261c0e23f2f0027d83aea11aac1c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Asian Continental Ancestry Group - genetics</topic><topic>Cervical cancer</topic><topic>Clinical outcomes</topic><topic>DNA Mutational Analysis</topic><topic>DNA, Neoplasm - genetics</topic><topic>DNA, Neoplasm - isolation & purification</topic><topic>Female</topic><topic>Humans</topic><topic>Middle Aged</topic><topic>Papillomaviridae - genetics</topic><topic>Papillomavirus Infections - enzymology</topic><topic>Papillomavirus Infections - genetics</topic><topic>Papillomavirus Infections - pathology</topic><topic>Papillomavirus Infections - virology</topic><topic>Predictive Value of Tests</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>STK11 genomic alterations</topic><topic>Uterine Cervical Neoplasms - enzymology</topic><topic>Uterine Cervical Neoplasms - genetics</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Uterine Cervical Neoplasms - virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hirose, Sou</creatorcontrib><creatorcontrib>Murakami, Naoya</creatorcontrib><creatorcontrib>Takahashi, Kazuaki</creatorcontrib><creatorcontrib>Kuno, Ikumi</creatorcontrib><creatorcontrib>Takayanagi, Daisuke</creatorcontrib><creatorcontrib>Asami, Yuka</creatorcontrib><creatorcontrib>Matsuda, Maiko</creatorcontrib><creatorcontrib>Shimada, Yoko</creatorcontrib><creatorcontrib>Yamano, Shotaro</creatorcontrib><creatorcontrib>Sunami, Kuniko</creatorcontrib><creatorcontrib>Yoshida, Kazushi</creatorcontrib><creatorcontrib>Honda, Takayuki</creatorcontrib><creatorcontrib>Nakahara, Tomomi</creatorcontrib><creatorcontrib>Watanabe, Tomoko</creatorcontrib><creatorcontrib>Komatsu, Masaaki</creatorcontrib><creatorcontrib>Hamamoto, Ryuji</creatorcontrib><creatorcontrib>Kato, Mayumi Kobayashi</creatorcontrib><creatorcontrib>Matsumoto, Koji</creatorcontrib><creatorcontrib>Okuma, Kae</creatorcontrib><creatorcontrib>Kuroda, Takafumi</creatorcontrib><creatorcontrib>Okamoto, Aikou</creatorcontrib><creatorcontrib>Itami, Jun</creatorcontrib><creatorcontrib>Kohno, Takashi</creatorcontrib><creatorcontrib>Kato, Tomoyasu</creatorcontrib><creatorcontrib>Shiraishi, Kouya</creatorcontrib><creatorcontrib>Yoshida, Hiroshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gynecologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hirose, Sou</au><au>Murakami, Naoya</au><au>Takahashi, Kazuaki</au><au>Kuno, Ikumi</au><au>Takayanagi, Daisuke</au><au>Asami, Yuka</au><au>Matsuda, Maiko</au><au>Shimada, Yoko</au><au>Yamano, Shotaro</au><au>Sunami, Kuniko</au><au>Yoshida, Kazushi</au><au>Honda, Takayuki</au><au>Nakahara, Tomomi</au><au>Watanabe, Tomoko</au><au>Komatsu, Masaaki</au><au>Hamamoto, Ryuji</au><au>Kato, Mayumi Kobayashi</au><au>Matsumoto, Koji</au><au>Okuma, Kae</au><au>Kuroda, Takafumi</au><au>Okamoto, Aikou</au><au>Itami, Jun</au><au>Kohno, Takashi</au><au>Kato, Tomoyasu</au><au>Shiraishi, Kouya</au><au>Yoshida, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients</atitle><jtitle>Gynecologic oncology</jtitle><addtitle>Gynecol Oncol</addtitle><date>2020-01</date><risdate>2020</risdate><volume>156</volume><issue>1</issue><spage>203</spage><epage>210</epage><pages>203-210</pages><issn>0090-8258</issn><eissn>1095-6859</eissn><abstract>Cervical cancer is the fourth most common cause of cancer-related deaths in Asian women, due to its poor prognosis. This study aimed to decipher genomic alteration profiles of a cohort of Japanese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and their prognostic significance.
During 2008–2018, 154 cervical cancer patients underwent a potentially curative resection procedure at the National Cancer Center Hospital. Genomic DNA samples were analyzed using Ion AmpliSeq™ Cancer Hotspot Panel v2. Alterations in the copy number of PIK3CA, ERBB2, PTEN, and STK11 were detected using the TaqMan assay. HPV-positive results were confirmed by genomic testing and in situ hybridization assay.
The frequency of genomic alterations in PIK3CA (36%), STK11 (16%), PTEN (11%), TP53 (11%), and KRAS (8%) was >5%. KRAS mutations were preferentially detected in patients with adenocarcinomas, and the frequency of PIK3CA mutations in patients with squamous cell carcinomas was higher than that in patients with other histological cancer types. HPV-positive results were observed in 139/154 (90.3%) patients, and TP53 mutants were detected in HPV-negative specimens. In this study, the overall survival of patients with genomic alterations in STK11 was worse than in patients with wild–type STK11 (hazard ratio = 10.6, P = 0.0079) and TCGA dataset (hazard ratio = 2.46, P = 0.029).
More than one-third of Japanese cervical cancer patients exhibit mutations targeted by molecular targeted therapies. We have proposed the prognostic value of STK11 genomic alterations.
•Specific genomic alteration profiles were observed in cervical cancer (CC) patients.•These were correlated with certain histological types and HPV genotypes.•We detected actionable genomic alterations in 54 (35%) cervical cancer patients.•STK11 genomic alterations caused a worse prognosis in cervical cancer patients.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>31757465</pmid><doi>10.1016/j.ygyno.2019.10.022</doi><tpages>8</tpages></addata></record> |
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| ispartof | Gynecologic oncology, 2020-01, Vol.156 (1), p.203-210 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Asian Continental Ancestry Group - genetics Cervical cancer Clinical outcomes DNA Mutational Analysis DNA, Neoplasm - genetics DNA, Neoplasm - isolation & purification Female Humans Middle Aged Papillomaviridae - genetics Papillomavirus Infections - enzymology Papillomavirus Infections - genetics Papillomavirus Infections - pathology Papillomavirus Infections - virology Predictive Value of Tests Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism STK11 genomic alterations Uterine Cervical Neoplasms - enzymology Uterine Cervical Neoplasms - genetics Uterine Cervical Neoplasms - pathology Uterine Cervical Neoplasms - virology |
| title | Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients |
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