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Intratumor heterogeneity in HCC.

Friemel J, Frick L, Weber A - Aging (Albany NY) (2015)

View Article: PubMed Central - PubMed

Affiliation: Institute of Surgical Pathology, University and University Hospital Zurich, 8091 Zurich, Switzerland.

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Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide, generally arising on the background of chronic liver diseases such as chronic viral hepatitis, alcohol-induced liver injury, or fatty liver disease... Clonal, i.e. genetic diversification was determined by sequencing the two most important HCC driver genes (TP53 and CTNNB1)... Combining Sanger sequencing with deep sequencing techniques facilitated the discovery of low frequency mutations and mitigated the effect of wild-type contamination... Thus, already analysis of the two main HCC driver genes clearly revealed that mutations are not homogeneously present in all regions of an individual tumor... This was found especially for CTNNB1 mutations, but also for TP53 mutations... The thorough dissection of morphologic, immunohistochemical and genomic intratumor hetero-geneity in our study illustrates that the primary co-existence of different growth patterns can be associated with divers biomarker expression and TP53 or CTNNB1 gene mutations among wild type tumor cells... The histopathologic and molecular classification of a tumor, often determined by the mutational status of a certain target, has therapeutic implications, e.g. in colorectal cancer (EGFR) or gastrointestinal stroma tumors (c-KIT)... In the era of targeted therapies, intratumor heterogeneity is a major challenge to successful cancer therapy since it may result in primary resistance or early evasion of treatment to chemotherapeutic or molecular targeted substances... This recomposition of the microenviroment can contribute to cancer evolution and therapy resistance... In conclusion, determining the degree of intratumor heterogeneity might be seen as a biomarker by itself and have prognostic value for disease progression... With the high-throughput techniques widely available now, we envision the systematic investigation of intratumor heterogeneity in different types of cancer in order to pinpoint its clinical relevance.

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Implications of HCC intratumor heterogeneity for tumor classification and targeted therapy. A biopsy taken from tumor area 2 does not necessarily represent the whole tumor. This may result in a short falling tumor classification as type B, and potentially in an incomplete therapy response due to sensitivity of only one tumor subclone (mutation B, biomarker B‘, pink).
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Figure 1: Implications of HCC intratumor heterogeneity for tumor classification and targeted therapy. A biopsy taken from tumor area 2 does not necessarily represent the whole tumor. This may result in a short falling tumor classification as type B, and potentially in an incomplete therapy response due to sensitivity of only one tumor subclone (mutation B, biomarker B‘, pink).


Intratumor heterogeneity in HCC.

Friemel J, Frick L, Weber A - Aging (Albany NY) (2015)

Implications of HCC intratumor heterogeneity for tumor classification and targeted therapy. A biopsy taken from tumor area 2 does not necessarily represent the whole tumor. This may result in a short falling tumor classification as type B, and potentially in an incomplete therapy response due to sensitivity of only one tumor subclone (mutation B, biomarker B‘, pink).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4505157&req=5

Figure 1: Implications of HCC intratumor heterogeneity for tumor classification and targeted therapy. A biopsy taken from tumor area 2 does not necessarily represent the whole tumor. This may result in a short falling tumor classification as type B, and potentially in an incomplete therapy response due to sensitivity of only one tumor subclone (mutation B, biomarker B‘, pink).

View Article: PubMed Central - PubMed

Affiliation: Institute of Surgical Pathology, University and University Hospital Zurich, 8091 Zurich, Switzerland.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide, generally arising on the background of chronic liver diseases such as chronic viral hepatitis, alcohol-induced liver injury, or fatty liver disease... Clonal, i.e. genetic diversification was determined by sequencing the two most important HCC driver genes (TP53 and CTNNB1)... Combining Sanger sequencing with deep sequencing techniques facilitated the discovery of low frequency mutations and mitigated the effect of wild-type contamination... Thus, already analysis of the two main HCC driver genes clearly revealed that mutations are not homogeneously present in all regions of an individual tumor... This was found especially for CTNNB1 mutations, but also for TP53 mutations... The thorough dissection of morphologic, immunohistochemical and genomic intratumor hetero-geneity in our study illustrates that the primary co-existence of different growth patterns can be associated with divers biomarker expression and TP53 or CTNNB1 gene mutations among wild type tumor cells... The histopathologic and molecular classification of a tumor, often determined by the mutational status of a certain target, has therapeutic implications, e.g. in colorectal cancer (EGFR) or gastrointestinal stroma tumors (c-KIT)... In the era of targeted therapies, intratumor heterogeneity is a major challenge to successful cancer therapy since it may result in primary resistance or early evasion of treatment to chemotherapeutic or molecular targeted substances... This recomposition of the microenviroment can contribute to cancer evolution and therapy resistance... In conclusion, determining the degree of intratumor heterogeneity might be seen as a biomarker by itself and have prognostic value for disease progression... With the high-throughput techniques widely available now, we envision the systematic investigation of intratumor heterogeneity in different types of cancer in order to pinpoint its clinical relevance.

No MeSH data available.


Related in: MedlinePlus