| 1. |
- Grundberg, Ida, et al.
(författare)
-
In situ mutation detection and visualization of intratumor heterogeneity for cancer research and diagnostics
- 2013
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 4:12, s. 2407-2418
-
Tidskriftsartikel (refereegranskat)abstract
- Current assays for somatic mutation analysis are based on extracts from tissue sections that often contain morphologically heterogeneous neoplastic regions with variable contents of genetically normal stromal and inflammatory cells, obscuring the results of the assays. We have developed an RNA-based in situ mutation assay that targets oncogenic mutations in a multiplex fashion that resolves the heterogeneity of the tissue sample. Activating oncogenic mutations are targets for a new generation of cancer drugs. For anti-EGFR therapy prediction, we demonstrate reliable in situ detection of KRAS mutations in codon 12 and 13 in colon and lung cancers in three different types of routinely processed tissue materials. High-throughput screening of KRAS mutation status was successfully performed on a tissue microarray. Moreover, we show how the patterns of expressed mutated and wild-type alleles can be studied in situ in tumors with complex combinations of mutated EGFR, KRAS and TP53. This in situ method holds great promise as a tool to investigate the role of somatic mutations during tumor progression and for prediction of response to targeted therapy.
|
|
| 2. |
- Mattsson, Johanna Sofia Margareta, et al.
(författare)
-
Consistent mutation status within histologically heterogeneous lung cancer lesions
- 2012
-
Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 61:4, s. 744-748
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Activating epidermal growth factor receptor (EGFR) and KRAS mutations characterize molecular subgroups of non-small-cell lung cancer (NSCLC) with a strong predictive value for response to EGFR inhibitor therapy. However, the temporal occurrence and clonal stability of these mutations during the course of cancer progression are debated. The aim of this study was to characterize the presence of EGFR and KRAS mutations in histologically different areas of primary NSCLC lesions. Methods and results: Formalin-fixed paraffin-embedded cancer specimens from six cases with EGFR mutations and five cases with KRAS mutations were selected from a pool of primary resected NSCLC patients. From each tumour, three morphologically distinct areas were manually microdissected and analysed for the presence of mutations. The results demonstrated consistent EGFR and KRAS mutation status in the different histological areas of all primary tumours. Conclusions: The results support the concept that activating EGFR and KRAS mutations are oncogenic events that are consistently present throughout the primary tumour independently of histological heterogeneity. Thus, for molecular diagnostics, any part of the tumour is likely to be representative for EGFR and KRAS mutation testing.
|
|
| 3. |
|
|
