Evolving concepts of tumor heterogeneity

Zellmer, Victoria R.; Zhang, Siyuan

doi:10.1186/2045-3701-4-69

Cited by 72 publications

(49 citation statements)

References 82 publications

(99 reference statements)

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“…Intratumor heterogeneity can be subdivided into spatial and temporal heterogeneity [4]. Spatial heterogeneity refers to differences that can be observed within a single tumor, i.e., either different genetic subpopulations within the primary tumor site or differences between the primary tumor and its metastatic lesions [5, 6]. Temporal heterogeneity refers to the dynamic nature of CRC, with genetic alterations developing within individual tumors over time.…”

Section: Introductionmentioning

confidence: 99%

Tumor Heterogeneity in Colorectal Cancer: What Do We Know So Far?

Sagaert¹,

Vanstapel²,

Verbeek³

2018

Pathobiology

138

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Colorectal cancer is not one disease but rather a collection of neoplastic diseases. Due to heterogeneity in the disease biology, therapy response, and prognosis, extensive disease stratification is required. Therefore, TNM stage, microsatellite status, tumor grade, lymphovascular invasion, and other parameters are assessed in the pathology report to indicate the extent and prognosis of the disease. The mutation status of KRAS, BRAF, and NRAS is also investigated in a metastatic context to predict the response to anti-EGFR therapy. Recently, 4 distinct molecular subtypes of colorectal cancer have been described that have both prognostic and therapeutic relevance. In addition, characterization of the inflammatory infiltrate revealed major differences in the amount and location of inflammatory cells in distinct colorectal tumor types. Together, all of these parameters help to stratify patients into different therapeutic and prognostic subgroups. However, this stratification is not unambiguous since tumors often display intratumoral heterogeneity, whereby several subpopulations within one tumor show differences in morphology, inflammatory infiltrate, mutational status, or gene expression profile. This article gives an overview of all of the current known data with regard to tumor heterogeneity at both inter- and intratumoral levels.

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Section: Introductionmentioning

confidence: 99%

Tumor Heterogeneity in Colorectal Cancer: What Do We Know So Far?

Sagaert¹,

Vanstapel²,

Verbeek³

2018

Pathobiology

138

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“…Because of intratumor heterogeneity, tumors intrinsically contain various mutations (17,18). After exposure to radiation, it can be presumed that cancer cells with radiation-sensitive mutations are eradicated, and cancer cells with radiationresistant mutations survive.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of radiation-resistant clones by a serial study of intratumor heterogeneity before and after stereotactic radiotherapy in lung cancer

et al. 2017

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Stereotactic radiotherapy (SRT) for inoperable stage I non-small cell lung cancer has shown promising results and is now an alternative therapy for this disease. Several reports have detailed changes in mutation profiles after treatment with chemotherapy; however, such changes after SRT for lung cancer have not been reported. A patient who received SRT for lung cancer developed local recurrence 9 months after treatment and underwent surgery in our department. Using bronchoscopically biopsied and surgically resected specimens, we performed targeted sequencing of 53 lung cancer-related genes and compared the tumor mutation profiles before and after SRT. Identical mutations were detected from tumor specimens collected before and after SRT, and the specimens were confirmed to be clonal. However, the number of mutations decreased after SRT, suggesting that it induced mutation selection. Analyses of the statistical inference of clonal population structure showed that this evolving heterogeneous genomic landscape may be caused by heterogeneous responsiveness to SRT.

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“…More recently, NGS technologies have been used to understand the breadth and depth of this overwhelming genetic diversity in primary and the metastatic tumours (74)(75)(76)(77)(78)(79). NGS and bioinformatic strategies have been developed and applied to tumour tissue, which have allowed both a measure of heterogeneity and the generation of phylogenetic models which provide a picture of the inferred development and branched evolution of the tumour (78,(80)(81)(82).…”

Section: Tumour and Ctc Heterogeneitymentioning

confidence: 99%