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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Intratumor heterogeneity (ITH) of premalignant colorectal lesions is an important area of research for understanding the diverse biological behavior of colorectal cancer (CRC). Accurate assessment of ITH depends substantially on the sampling strategy used. We present a novel methodological approach termed whole tumor heterogeneity topography (WTHT) and compare it with three previously described sampling strategies: whole tumor homogenization, macrodissection of selected tumor regions, and multisampling. A cohort of 184 advanced precancerous colorectal lesions was processed into paraffin blocks, and the entire tumor mass was systematically divided into equally sized samples (~10 mm3). DNA was isolated from each sample separately and analyzed for hotspot mutations in APC, KRAS, BRAF, PIK3CA, and TP53. ITH was quantified using mutation variance and a newly introduced Heterogeneity Grade (HG). Results obtained by WTHT were statistically and graphically compared with three other modeled sampling strategies. Significant differences were observed among the analyzed sampling approaches. Macrodissection showed the greatest deviation from WTHT, indicating substantial sampling bias, whereas multisampling produced the closest results. WTHT enabled precise quantification and spatial mapping of mutational clones across the entire lesion. WTHT combined with HG provides a robust and reproducible framework for comprehensive assessment of ITH in colorectal adenomas.<\/jats:p>","DOI":"10.3390\/ijms27156547","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:11:26Z","timestamp":1784797886000},"page":"6547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Whole Tumor Heterogeneity Topography (WTHT)\u2014A New Approach for Assessment of Intratumor Mutational Heterogeneity in Colorectal Adenomas"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2985-7145","authenticated-orcid":false,"given":"Tereza","family":"Halkova","sequence":"first","affiliation":[{"name":"Centre for Applied Genomics of Solid Tumors (CEGES), Genomac Research Institute, Drnovsk\u00e1 1112\/60, 161 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1650-760X","authenticated-orcid":false,"given":"Lucia","family":"Hodasova Pauerova","sequence":"additional","affiliation":[{"name":"Centre for Applied Genomics of Solid Tumors (CEGES), Genomac Research Institute, Drnovsk\u00e1 1112\/60, 161 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Blechova","sequence":"additional","affiliation":[{"name":"Centre for Applied Genomics of Solid Tumors (CEGES), Genomac Research Institute, Drnovsk\u00e1 1112\/60, 161 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza","family":"Benesova","sequence":"additional","affiliation":[{"name":"Centre for Applied Genomics of Solid Tumors (CEGES), Genomac Research Institute, Drnovsk\u00e1 1112\/60, 161 00 Prague, Czech 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Pathology, Military University Hospital Prague, U Vojenske Nemocnice 1200, 169 02 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1385-7655","authenticated-orcid":false,"given":"Katerina","family":"Hejcmanova","sequence":"additional","affiliation":[{"name":"Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, 601 77 Brno, Czech Republic"},{"name":"Institute of Health Information and Statistics of the Czech Republic, 128 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Ngo","sequence":"additional","affiliation":[{"name":"Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, 601 77 Brno, Czech Republic"},{"name":"Institute of Health Information and Statistics of the Czech Republic, 128 00 Prague, Czech 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