Rapid assessment of 3-dimensional intra-tumor heterogeneity through cycling temperature capillary electrophoresis
Abstract Objective Tumors are heterogeneous three-dimensional masses populated by numerous cell types, including distinct sub-clones of cancerous cells. Various sub-clones within the same tumor mass may respond differently to cancer treatment, and intra-tumor heterogeneity contributes to acquired th...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-08-01
|
| Series: | BMC Research Notes |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13104-023-06437-5 |
| _version_ | 1797453995390795776 |
|---|---|
| author | Anna Połeć Per Olaf Ekstrøm Christian Fougner Therese Sørlie Jens Henrik Norum |
| author_facet | Anna Połeć Per Olaf Ekstrøm Christian Fougner Therese Sørlie Jens Henrik Norum |
| author_sort | Anna Połeć |
| collection | DOAJ |
| description | Abstract Objective Tumors are heterogeneous three-dimensional masses populated by numerous cell types, including distinct sub-clones of cancerous cells. Various sub-clones within the same tumor mass may respond differently to cancer treatment, and intra-tumor heterogeneity contributes to acquired therapeutic resistance. Thus, one tissue biopsy will in most cases not be representative of the entire genetic landscape of a tumor mass. In this study, we aimed to establish an easily accessible, low cost method to address intra-tumor heterogeneity in three dimensions, for a limited number of DNA alterations. Results This study includes analyses of the three-dimensional (3D) distribution of DNA mutations in human colon cancer and mouse mammary gland tumor tissue samples. We used laser capture microdissection for the unbiased collection of tissue in several XY-planes throughout the tumor masses. Cycling temperature capillary electrophoresis was used to determine mutant allele frequency. High-resolution distribution maps of KRAS and Trp53 mutations were generated for each XY-plane in human and mouse tumor samples, respectively. To provide a holistic interpretation of the mutation distribution, we generated interactive 3D heatmaps giving an easily interpretable understanding of the spatial distribution of the analyzed mutations. The method described herein provides an accessible way of describing intra-tumor heterogeneity for a limited number of mutations. |
| first_indexed | 2024-03-09T15:30:51Z |
| format | Article |
| id | doaj.art-176a176885cb4c47a1de5292eb97ff36 |
| institution | Directory Open Access Journal |
| issn | 1756-0500 |
| language | English |
| last_indexed | 2024-03-09T15:30:51Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Research Notes |
| spelling | doaj.art-176a176885cb4c47a1de5292eb97ff362023-11-26T12:14:33ZengBMCBMC Research Notes1756-05002023-08-011611810.1186/s13104-023-06437-5Rapid assessment of 3-dimensional intra-tumor heterogeneity through cycling temperature capillary electrophoresisAnna Połeć0Per Olaf Ekstrøm1Christian Fougner2Therese Sørlie3Jens Henrik Norum4Department of Cancer Genetics, Institute for Cancer Research, Radium Hospital, Oslo University HospitalDepartment of Tumor Biology, Institute for Cancer Research, Radium Hospital, Oslo University HospitalDepartment of Cancer Genetics, Institute for Cancer Research, Radium Hospital, Oslo University HospitalDepartment of Cancer Genetics, Institute for Cancer Research, Radium Hospital, Oslo University HospitalDepartment of Cancer Genetics, Institute for Cancer Research, Radium Hospital, Oslo University HospitalAbstract Objective Tumors are heterogeneous three-dimensional masses populated by numerous cell types, including distinct sub-clones of cancerous cells. Various sub-clones within the same tumor mass may respond differently to cancer treatment, and intra-tumor heterogeneity contributes to acquired therapeutic resistance. Thus, one tissue biopsy will in most cases not be representative of the entire genetic landscape of a tumor mass. In this study, we aimed to establish an easily accessible, low cost method to address intra-tumor heterogeneity in three dimensions, for a limited number of DNA alterations. Results This study includes analyses of the three-dimensional (3D) distribution of DNA mutations in human colon cancer and mouse mammary gland tumor tissue samples. We used laser capture microdissection for the unbiased collection of tissue in several XY-planes throughout the tumor masses. Cycling temperature capillary electrophoresis was used to determine mutant allele frequency. High-resolution distribution maps of KRAS and Trp53 mutations were generated for each XY-plane in human and mouse tumor samples, respectively. To provide a holistic interpretation of the mutation distribution, we generated interactive 3D heatmaps giving an easily interpretable understanding of the spatial distribution of the analyzed mutations. The method described herein provides an accessible way of describing intra-tumor heterogeneity for a limited number of mutations.https://doi.org/10.1186/s13104-023-06437-5Laser capture microdissectionCycling temperature capillary electrophoresisIntra-tumor heterogeneity3D modeling |
| spellingShingle | Anna Połeć Per Olaf Ekstrøm Christian Fougner Therese Sørlie Jens Henrik Norum Rapid assessment of 3-dimensional intra-tumor heterogeneity through cycling temperature capillary electrophoresis BMC Research Notes Laser capture microdissection Cycling temperature capillary electrophoresis Intra-tumor heterogeneity 3D modeling |
| title | Rapid assessment of 3-dimensional intra-tumor heterogeneity through cycling temperature capillary electrophoresis |
| title_full | Rapid assessment of 3-dimensional intra-tumor heterogeneity through cycling temperature capillary electrophoresis |
| title_fullStr | Rapid assessment of 3-dimensional intra-tumor heterogeneity through cycling temperature capillary electrophoresis |
| title_full_unstemmed | Rapid assessment of 3-dimensional intra-tumor heterogeneity through cycling temperature capillary electrophoresis |
| title_short | Rapid assessment of 3-dimensional intra-tumor heterogeneity through cycling temperature capillary electrophoresis |
| title_sort | rapid assessment of 3 dimensional intra tumor heterogeneity through cycling temperature capillary electrophoresis |
| topic | Laser capture microdissection Cycling temperature capillary electrophoresis Intra-tumor heterogeneity 3D modeling |
| url | https://doi.org/10.1186/s13104-023-06437-5 |
| work_keys_str_mv | AT annapołec rapidassessmentof3dimensionalintratumorheterogeneitythroughcyclingtemperaturecapillaryelectrophoresis AT perolafekstrøm rapidassessmentof3dimensionalintratumorheterogeneitythroughcyclingtemperaturecapillaryelectrophoresis AT christianfougner rapidassessmentof3dimensionalintratumorheterogeneitythroughcyclingtemperaturecapillaryelectrophoresis AT theresesørlie rapidassessmentof3dimensionalintratumorheterogeneitythroughcyclingtemperaturecapillaryelectrophoresis AT jenshenriknorum rapidassessmentof3dimensionalintratumorheterogeneitythroughcyclingtemperaturecapillaryelectrophoresis |