{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:47:50Z","timestamp":1779104870055,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T00:00:00Z","timestamp":1511913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea","award":["0920050"],"award-info":[{"award-number":["0920050"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Genome\u2010wide next\u2010generation sequencing has revealed several driver mutations and has allowed the establishment of a molecular taxonomy of gastric cancer. However, there are few detailed studies on the mutational spectrum of poorly cohesive gastric carcinoma. Thus, this study aim to investigate its mutation profile based on clinicopathological characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Herein, we analysed the mutational pattern of 77 genes in a cohort of 91 patients with poorly cohesive carcinoma by using targeted sequencing, and evaluated the clinicopathological significance of the various mutations based on histological pattern, either signet ring cell (SRC) or other types of poorly cohesive carcinoma (not otherwise specified) (PCC\u2010NOS). Panels of seven (<jats:italic>PIK3CA<\/jats:italic>,<jats:italic> CDH1<\/jats:italic>,<jats:italic> PTEN<\/jats:italic>,<jats:italic> RHOA<\/jats:italic>,<jats:italic> HDCA9<\/jats:italic>,<jats:italic> KRAS<\/jats:italic>, and <jats:italic>ATM<\/jats:italic>), three (<jats:italic>PIK3CA<\/jats:italic>,<jats:italic> CTNNB1<\/jats:italic>, and <jats:italic>KRAS<\/jats:italic>) and two (<jats:italic>HDCA9<\/jats:italic> and <jats:italic>IGF1R<\/jats:italic>) genes were associated with a diffuse infiltrative growth pattern, lymphovascular invasion, and perineural invasion, respectively. Furthermore, <jats:italic>PDGFRB<\/jats:italic> mutations were associated with a favourable prognosis, whereas <jats:italic>MET<\/jats:italic> mutations were associated with a poor prognosis. The PCC\u2010NOS\u2010predominant type was associated with a greater depth of invasion, lymph node metastasis and poorer prognosis than the SRC\u2010predominant type. Mutations in <jats:italic>TP53<\/jats:italic>,<jats:italic> BRAF<\/jats:italic>,<jats:italic> PI3CA<\/jats:italic>,<jats:italic> SMAD4<\/jats:italic> and <jats:italic>RHOA<\/jats:italic> were associated with PCC\u2010NOS. Interestingly, <jats:italic>RHOA<\/jats:italic>\u2010mutated gastric cancers showed a distinct morphology, as they were characterised by a superficial SRC or tubular component and a deep invasive PCC\u2010NOS component with desmoplasia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, our findings demonstrate that gastric poorly cohesive carcinomas show several mutational patterns associated with specific clinicopathological characteristics, and particularly show distinct morphological findings when associated with <jats:italic>RHOA<\/jats:italic> mutation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13383","type":"journal-article","created":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T14:38:43Z","timestamp":1504622323000},"page":"556-568","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Gastric poorly cohesive carcinoma: a correlative study of mutational signatures and prognostic significance based on histopathological subtypes"],"prefix":"10.1111","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-1570","authenticated-orcid":false,"given":"Chae H","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Pathology Pusan National University Hospital and Pusan National University School of Medicine Busan Korea"},{"name":"BioMedical Research Institute Pusan National University Hospital Busan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young K","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology Pusan National University Hospital and Pusan National University School of Medicine Busan Korea"},{"name":"BioMedical Research Institute Pusan National University Hospital Busan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sojeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology Pusan National University Hospital and Pusan National University School of Medicine Busan Korea"},{"name":"BioMedical Research Institute Pusan National University Hospital Busan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahrong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology Pusan National University Hospital and Pusan National University School of Medicine Busan Korea"},{"name":"BioMedical Research Institute Pusan National University Hospital Busan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye J","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology Pusan National University Hospital and Pusan National University School of Medicine Busan Korea"},{"name":"BioMedical Research Institute Pusan National University Hospital Busan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pathology Pusan National University Hospital and Pusan National University School of Medicine Busan Korea"},{"name":"BioMedical Research Institute Pusan National University Hospital Busan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeo J","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Pathology Pusan National University Hospital and Pusan National University School of Medicine Busan Korea"},{"name":"BioMedical Research Institute Pusan National University Hospital Busan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7641-1509","authenticated-orcid":false,"given":"Do Y","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology Pusan National University Hospital and Pusan National University School of Medicine Busan Korea"},{"name":"BioMedical Research Institute Pusan National University Hospital Busan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory Y","family":"Lauwers","sequence":"additional","affiliation":[{"name":"Department of Pathology H. Lee Moffitt Cancer Center and Research Institute Tampa FL 33162 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,29]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"GLOBOCAN 2012.Estimated cancer incidence mortality and prevalence worldwide in 2012. Available at:http:\/\/globocan.iarc.fr\/Pages\/fact_sheets_cancer.aspx"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm239"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13480"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3850"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2983"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/ng.2984","article-title":"Recurrent gain\u2010of\u2010function mutations of RHOA in diffuse\u2010type gastric carcinoma","volume":"46","author":"Kakiuchi M","year":"2014","journal-title":"Nat. Genet."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.1965.64.1.31"},{"key":"e_1_2_8_9_1","volume-title":"World Health Organization classification of tumours of the digestive system","author":"Bosman FT","year":"2010"},{"key":"e_1_2_8_10_1","volume-title":"American Joint Committee on Cancer Staging Manual","author":"Edge SB","year":"2009"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.4132\/KoreanJPathol.2013.47.1.28"},{"issue":"11","key":"e_1_2_8_12_1","first-page":"1","article-title":"Whole genome sequencing of 35 individuals provides insights into the genetic architecture of Korean population","volume":"15","author":"Zhang W","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1422640112"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10120"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2013.08.016"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i15.4020"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-015-0493-0"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2009.03.003"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-011-9396-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-2443"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","first-page":"e0143107","DOI":"10.1371\/journal.pone.0143407","article-title":"Functional characterization of germline mutations in PDGFB and PDGFRB in primary familial brain calcification","volume":"10","author":"Vanlandewijck M","year":"2015","journal-title":"PLoS ONE"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2010.01639.x"},{"key":"e_1_2_8_23_1","first-page":"1","article-title":"Met mutation and familial gastric cancer","volume":"38","author":"Chen JD","year":"2001","journal-title":"J. Med. Genet."},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203874"},{"key":"e_1_2_8_25_1","first-page":"1","article-title":"A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familiar gastric cancer","volume":"40","author":"Kim I","year":"2003","journal-title":"J. Med. Genet."},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-68"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.13383","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.13383","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T15:09:57Z","timestamp":1695740997000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.13383"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,29]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1111\/his.13383"],"URL":"https:\/\/doi.org\/10.1111\/his.13383","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,29]]},"assertion":[{"value":"2017-03-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-08-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}