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Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia
There is about three times higher incidence of young patients
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| Published in: | Cancers 2021-12, Vol.13 (24), p.6245 |
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| creator | Susanti, Susanti Wibowo, Satrio Akbariani, Gilang Yoshuantari, Naomi Heriyanto, Didik Setyo Ridwanuloh, Asep Muhamad Hariyatun, Hariyatun Handaya, Adeodatus Yuda Kurnianda, Johan Hutajulu, Susanna Hilda Ilyas, Mohammad |
| description | There is about three times higher incidence of young patients |
| doi_str_mv | 10.3390/cancers13246245 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8699188</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2612737899</sourcerecordid><originalsourceid>FETCH-LOGICAL-c421t-cdd13054c2aeae5862a157256b5a4d884a5610acd9c7d165ec3a5032d8d5a5e3</originalsourceid><addsrcrecordid>eNpdkctLJDEQxsOyi4rr2dsS8LKX0bw7fRFkWB8w4kHvoUxqZloyiSbdQv_3tjsqai4VqF999fgIOeTsWMqWnXhIHkvlUigjlP5B9gRrxMyYVv389N8lB7U-sOlJyRvT7JBdqVqlrDF7BK5zRD9EKPQsQRxrV2le0nmOuaDvIdL5tgu9HVYrrH2lQC-71ZqeF3waMPnxlV-Mya_p7ZhCyRukXaJXKeSEtYPf5NcSYsWDt7hP7s7_3c0vZ4ubi6v52WLmleD9zIfAJdPKC0BAbY0Arhuhzb0GFaxVoA1n4EPrm8CNRi9BMymCDRo0yn1yupV9HO43GDymvkB0j6XbQBldhs59zaRu7Vb52VnTttzaSeDvm0DJ02K1d5uueowREuahOmG4ErIRTE_o0Tf0IQ9lOt9_SjSysW07USdbypdca8HlxzCcuVcD3TcDp4o_n3f44N_tki8Od5jT</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2612737899</pqid></control><display><type>article</type><title>Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia</title><source>Open Access: PubMed Central</source><source>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</source><creator>Susanti, Susanti ; Wibowo, Satrio ; Akbariani, Gilang ; Yoshuantari, Naomi ; Heriyanto, Didik Setyo ; Ridwanuloh, Asep Muhamad ; Hariyatun, Hariyatun ; Handaya, Adeodatus Yuda ; Kurnianda, Johan ; Hutajulu, Susanna Hilda ; Ilyas, Mohammad</creator><creatorcontrib>Susanti, Susanti ; Wibowo, Satrio ; Akbariani, Gilang ; Yoshuantari, Naomi ; Heriyanto, Didik Setyo ; Ridwanuloh, Asep Muhamad ; Hariyatun, Hariyatun ; Handaya, Adeodatus Yuda ; Kurnianda, Johan ; Hutajulu, Susanna Hilda ; Ilyas, Mohammad</creatorcontrib><description>There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016-2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all-186/197 (99.45%)-MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as "Probable Lynch" (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%,
= 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both "Probable Lynch" and non-LS (sporadic) groups (
= 227) was comparable (
= 0.59), with follow up period of 0-1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (
< 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72-11.2;
= 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13246245</identifier><identifier>PMID: 34944866</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Cancer ; Capillary electrophoresis ; Colorectal cancer ; Colorectal carcinoma ; DNA methylation ; FLI-1 protein ; Genetic markers ; Genetic testing ; Microsatellites ; MLH1 protein ; Mortality ; Mutation ; Paraffin ; Patients ; Polymerase chain reaction ; Survival ; Tumors</subject><ispartof>Cancers, 2021-12, Vol.13 (24), p.6245</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-cdd13054c2aeae5862a157256b5a4d884a5610acd9c7d165ec3a5032d8d5a5e3</citedby><cites>FETCH-LOGICAL-c421t-cdd13054c2aeae5862a157256b5a4d884a5610acd9c7d165ec3a5032d8d5a5e3</cites><orcidid>0000-0002-8648-3677 ; 0000-0003-0256-1955</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2612737899/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2612737899?pq-origsite=primo$$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/34944866$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Susanti, Susanti</creatorcontrib><creatorcontrib>Wibowo, Satrio</creatorcontrib><creatorcontrib>Akbariani, Gilang</creatorcontrib><creatorcontrib>Yoshuantari, Naomi</creatorcontrib><creatorcontrib>Heriyanto, Didik Setyo</creatorcontrib><creatorcontrib>Ridwanuloh, Asep Muhamad</creatorcontrib><creatorcontrib>Hariyatun, Hariyatun</creatorcontrib><creatorcontrib>Handaya, Adeodatus Yuda</creatorcontrib><creatorcontrib>Kurnianda, Johan</creatorcontrib><creatorcontrib>Hutajulu, Susanna Hilda</creatorcontrib><creatorcontrib>Ilyas, Mohammad</creatorcontrib><title>Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016-2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all-186/197 (99.45%)-MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as "Probable Lynch" (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%,
= 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both "Probable Lynch" and non-LS (sporadic) groups (
= 227) was comparable (
= 0.59), with follow up period of 0-1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (
< 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72-11.2;
= 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West.</description><subject>Cancer</subject><subject>Capillary electrophoresis</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>DNA methylation</subject><subject>FLI-1 protein</subject><subject>Genetic markers</subject><subject>Genetic testing</subject><subject>Microsatellites</subject><subject>MLH1 protein</subject><subject>Mortality</subject><subject>Mutation</subject><subject>Paraffin</subject><subject>Patients</subject><subject>Polymerase chain reaction</subject><subject>Survival</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNpdkctLJDEQxsOyi4rr2dsS8LKX0bw7fRFkWB8w4kHvoUxqZloyiSbdQv_3tjsqai4VqF999fgIOeTsWMqWnXhIHkvlUigjlP5B9gRrxMyYVv389N8lB7U-sOlJyRvT7JBdqVqlrDF7BK5zRD9EKPQsQRxrV2le0nmOuaDvIdL5tgu9HVYrrH2lQC-71ZqeF3waMPnxlV-Mya_p7ZhCyRukXaJXKeSEtYPf5NcSYsWDt7hP7s7_3c0vZ4ubi6v52WLmleD9zIfAJdPKC0BAbY0Arhuhzb0GFaxVoA1n4EPrm8CNRi9BMymCDRo0yn1yupV9HO43GDymvkB0j6XbQBldhs59zaRu7Vb52VnTttzaSeDvm0DJ02K1d5uueowREuahOmG4ErIRTE_o0Tf0IQ9lOt9_SjSysW07USdbypdca8HlxzCcuVcD3TcDp4o_n3f44N_tki8Od5jT</recordid><startdate>20211213</startdate><enddate>20211213</enddate><creator>Susanti, Susanti</creator><creator>Wibowo, Satrio</creator><creator>Akbariani, Gilang</creator><creator>Yoshuantari, Naomi</creator><creator>Heriyanto, Didik Setyo</creator><creator>Ridwanuloh, Asep Muhamad</creator><creator>Hariyatun, Hariyatun</creator><creator>Handaya, Adeodatus Yuda</creator><creator>Kurnianda, Johan</creator><creator>Hutajulu, Susanna Hilda</creator><creator>Ilyas, Mohammad</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8648-3677</orcidid><orcidid>https://orcid.org/0000-0003-0256-1955</orcidid></search><sort><creationdate>20211213</creationdate><title>Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia</title><author>Susanti, Susanti ; Wibowo, Satrio ; Akbariani, Gilang ; Yoshuantari, Naomi ; Heriyanto, Didik Setyo ; Ridwanuloh, Asep Muhamad ; Hariyatun, Hariyatun ; Handaya, Adeodatus Yuda ; Kurnianda, Johan ; Hutajulu, Susanna Hilda ; Ilyas, Mohammad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-cdd13054c2aeae5862a157256b5a4d884a5610acd9c7d165ec3a5032d8d5a5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cancer</topic><topic>Capillary electrophoresis</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>DNA methylation</topic><topic>FLI-1 protein</topic><topic>Genetic markers</topic><topic>Genetic testing</topic><topic>Microsatellites</topic><topic>MLH1 protein</topic><topic>Mortality</topic><topic>Mutation</topic><topic>Paraffin</topic><topic>Patients</topic><topic>Polymerase chain reaction</topic><topic>Survival</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Susanti, Susanti</creatorcontrib><creatorcontrib>Wibowo, Satrio</creatorcontrib><creatorcontrib>Akbariani, Gilang</creatorcontrib><creatorcontrib>Yoshuantari, Naomi</creatorcontrib><creatorcontrib>Heriyanto, Didik Setyo</creatorcontrib><creatorcontrib>Ridwanuloh, Asep Muhamad</creatorcontrib><creatorcontrib>Hariyatun, Hariyatun</creatorcontrib><creatorcontrib>Handaya, Adeodatus Yuda</creatorcontrib><creatorcontrib>Kurnianda, Johan</creatorcontrib><creatorcontrib>Hutajulu, Susanna Hilda</creatorcontrib><creatorcontrib>Ilyas, Mohammad</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest research library</collection><collection>ProQuest Biological Science Journals</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Susanti, Susanti</au><au>Wibowo, Satrio</au><au>Akbariani, Gilang</au><au>Yoshuantari, Naomi</au><au>Heriyanto, Didik Setyo</au><au>Ridwanuloh, Asep Muhamad</au><au>Hariyatun, Hariyatun</au><au>Handaya, Adeodatus Yuda</au><au>Kurnianda, Johan</au><au>Hutajulu, Susanna Hilda</au><au>Ilyas, Mohammad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2021-12-13</date><risdate>2021</risdate><volume>13</volume><issue>24</issue><spage>6245</spage><pages>6245-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016-2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all-186/197 (99.45%)-MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as "Probable Lynch" (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%,
= 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both "Probable Lynch" and non-LS (sporadic) groups (
= 227) was comparable (
= 0.59), with follow up period of 0-1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (
< 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72-11.2;
= 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>34944866</pmid><doi>10.3390/cancers13246245</doi><orcidid>https://orcid.org/0000-0002-8648-3677</orcidid><orcidid>https://orcid.org/0000-0003-0256-1955</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancers, 2021-12, Vol.13 (24), p.6245 |
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| subjects | Cancer Capillary electrophoresis Colorectal cancer Colorectal carcinoma DNA methylation FLI-1 protein Genetic markers Genetic testing Microsatellites MLH1 protein Mortality Mutation Paraffin Patients Polymerase chain reaction Survival Tumors |
| title | Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia |
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