{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:33:49Z","timestamp":1789785229797,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T00:00:00Z","timestamp":1461715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2016,6]]},"abstract":"Although most sporadic colorectal cancers (CRC<\/jats:styled-content>) are thought to develop from protruded adenomas through the adenoma\u2013carcinoma sequence, some CRC<\/jats:styled-content> develop through flat lesions, so\u2010called laterally spreading tumors (LST<\/jats:styled-content>). We previously analyzed epigenetic aberrations in LST<\/jats:styled-content> and found that LST<\/jats:styled-content> are clearly classified into two molecular subtypes: intermediate\u2010methylation with KRAS<\/jats:styled-content><\/jats:italic> mutation and low\u2010methylation with absence of oncogene mutation. Intermediate\u2010methylation LST<\/jats:styled-content> were mostly granular type LST<\/jats:styled-content> (LST<\/jats:styled-content>\u2010G) and low\u2010methylation LST<\/jats:styled-content> were mostly non\u2010granular LST<\/jats:styled-content> (LST<\/jats:styled-content>\u2010NG<\/jats:styled-content>). In the present study, we conducted a targeted exon sequencing study including 38 candidate CRC<\/jats:styled-content> driver genes to gain insight into how these genes modulate the development of LST<\/jats:styled-content>. We identified a mean of 11.5 suspected nonpolymorphic variants per sample, including indels and non\u2010synonymous mutations, although there was no significant difference in the frequency of total mutations between LST<\/jats:styled-content>\u2010G and LST<\/jats:styled-content>\u2010NG<\/jats:styled-content>. Genes associated with RTK<\/jats:styled-content>\/RAS<\/jats:styled-content> signaling pathway were mutated more frequently in LST<\/jats:styled-content>\u2010G than LST<\/jats:styled-content>\u2010NG<\/jats:styled-content> (P<\/jats:italic> = 0.004), especially KRAS<\/jats:styled-content><\/jats:italic> mutation occurring at 70% (30\/43) of LST<\/jats:styled-content>\u2010G but 26% (13\/50) of LST<\/jats:styled-content>\u2010NG<\/jats:styled-content> (P<\/jats:italic> < 0.0001). Both LST<\/jats:styled-content> showed high frequency of APC<\/jats:styled-content><\/jats:italic> mutation, even at adenoma stage, suggesting its involvement in the initiation stage of LST<\/jats:styled-content>, as it is involved at early stage of colorectal carcinogenesis via adenoma\u2010carcinoma sequence. TP<\/jats:styled-content>53<\/jats:italic> mutation was never observed in adenomas, but was specifically detected in cancer samples. TP<\/jats:styled-content>53<\/jats:italic> mutation occurred during development of intramucosal cancer in LST<\/jats:styled-content>\u2010NG<\/jats:styled-content>, but during development of cancer with submucosal invasion in LST<\/jats:styled-content>\u2010G. It is suggested that TP<\/jats:styled-content>53<\/jats:italic> mutation occurs in the early stages of cancer development from adenoma in both LST<\/jats:styled-content>\u2010G and LST<\/jats:styled-content>\u2010NG<\/jats:styled-content>, but is involved at an earlier stage in LST<\/jats:styled-content>\u2010NG<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cas.12930","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T02:17:20Z","timestamp":1458353840000},"page":"820-827","source":"Crossref","is-referenced-by-count":20,"title":["TP<\/scp>53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors"],"prefix":"10.1111","volume":"107","author":[{"given":"Eiji","family":"Sakai","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yokohama City University School of Medicine Yokohama Japan"},{"name":"Department of Molecular Oncology Graduate School of Medicine Chiba 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