Advanced Intestinal Cancers often Maintain a Multi-Ancestral Architecture.
A widely accepted paradigm in the field of cancer biology is that solid tumors are uni-ancestral being derived from a single founder and its descendants. However, data have been steadily accruing that indicate early tumors in mice and humans can have a multi-ancestral origin in which an initiated pr...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4769224?pdf=render |
| _version_ | 1818310238850252800 |
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| author | Christopher D Zahm Joseph M Szulczewski Alyssa A Leystra Terrah J Paul Olson Linda Clipson Dawn M Albrecht Malisa Middlebrooks Andrew T Thliveris Kristina A Matkowskyj Mary Kay Washington Michael A Newton Kevin W Eliceiri Richard B Halberg |
| author_facet | Christopher D Zahm Joseph M Szulczewski Alyssa A Leystra Terrah J Paul Olson Linda Clipson Dawn M Albrecht Malisa Middlebrooks Andrew T Thliveris Kristina A Matkowskyj Mary Kay Washington Michael A Newton Kevin W Eliceiri Richard B Halberg |
| author_sort | Christopher D Zahm |
| collection | DOAJ |
| description | A widely accepted paradigm in the field of cancer biology is that solid tumors are uni-ancestral being derived from a single founder and its descendants. However, data have been steadily accruing that indicate early tumors in mice and humans can have a multi-ancestral origin in which an initiated primogenitor facilitates the transformation of neighboring co-genitors. We developed a new mouse model that permits the determination of clonal architecture of intestinal tumors in vivo and ex vivo, have validated this model, and then used it to assess the clonal architecture of adenomas, intramucosal carcinomas, and invasive adenocarcinomas of the intestine. The percentage of multi-ancestral tumors did not significantly change as tumors progressed from adenomas with low-grade dysplasia [40/65 (62%)], to adenomas with high-grade dysplasia [21/37 (57%)], to intramucosal carcinomas [10/23 (43%]), to invasive adenocarcinomas [13/19 (68%)], indicating that the clone arising from the primogenitor continues to coexist with clones arising from co-genitors. Moreover, neoplastic cells from distinct clones within a multi-ancestral adenocarcinoma have even been observed to simultaneously invade into the underlying musculature [2/15 (13%)]. Thus, intratumoral heterogeneity arising early in tumor formation persists throughout tumorigenesis. |
| first_indexed | 2024-12-13T07:42:54Z |
| format | Article |
| id | doaj.art-2e3dbb4f216143749f8ae0706d841ae3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T07:42:54Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2e3dbb4f216143749f8ae0706d841ae32022-12-21T23:54:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e015017010.1371/journal.pone.0150170Advanced Intestinal Cancers often Maintain a Multi-Ancestral Architecture.Christopher D ZahmJoseph M SzulczewskiAlyssa A LeystraTerrah J Paul OlsonLinda ClipsonDawn M AlbrechtMalisa MiddlebrooksAndrew T ThliverisKristina A MatkowskyjMary Kay WashingtonMichael A NewtonKevin W EliceiriRichard B HalbergA widely accepted paradigm in the field of cancer biology is that solid tumors are uni-ancestral being derived from a single founder and its descendants. However, data have been steadily accruing that indicate early tumors in mice and humans can have a multi-ancestral origin in which an initiated primogenitor facilitates the transformation of neighboring co-genitors. We developed a new mouse model that permits the determination of clonal architecture of intestinal tumors in vivo and ex vivo, have validated this model, and then used it to assess the clonal architecture of adenomas, intramucosal carcinomas, and invasive adenocarcinomas of the intestine. The percentage of multi-ancestral tumors did not significantly change as tumors progressed from adenomas with low-grade dysplasia [40/65 (62%)], to adenomas with high-grade dysplasia [21/37 (57%)], to intramucosal carcinomas [10/23 (43%]), to invasive adenocarcinomas [13/19 (68%)], indicating that the clone arising from the primogenitor continues to coexist with clones arising from co-genitors. Moreover, neoplastic cells from distinct clones within a multi-ancestral adenocarcinoma have even been observed to simultaneously invade into the underlying musculature [2/15 (13%)]. Thus, intratumoral heterogeneity arising early in tumor formation persists throughout tumorigenesis.http://europepmc.org/articles/PMC4769224?pdf=render |
| spellingShingle | Christopher D Zahm Joseph M Szulczewski Alyssa A Leystra Terrah J Paul Olson Linda Clipson Dawn M Albrecht Malisa Middlebrooks Andrew T Thliveris Kristina A Matkowskyj Mary Kay Washington Michael A Newton Kevin W Eliceiri Richard B Halberg Advanced Intestinal Cancers often Maintain a Multi-Ancestral Architecture. PLoS ONE |
| title | Advanced Intestinal Cancers often Maintain a Multi-Ancestral Architecture. |
| title_full | Advanced Intestinal Cancers often Maintain a Multi-Ancestral Architecture. |
| title_fullStr | Advanced Intestinal Cancers often Maintain a Multi-Ancestral Architecture. |
| title_full_unstemmed | Advanced Intestinal Cancers often Maintain a Multi-Ancestral Architecture. |
| title_short | Advanced Intestinal Cancers often Maintain a Multi-Ancestral Architecture. |
| title_sort | advanced intestinal cancers often maintain a multi ancestral architecture |
| url | http://europepmc.org/articles/PMC4769224?pdf=render |
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