Midtveisevaluering - Deepak Poduval

ABSTRAKT

Biomarkers in advanced Cancers

Novel miRNAs in locally advanced breast cancer and intermetastatic heterogeneity in melanoma and colon cancer

Human cancers differ in rates of growth; differentiation and cell proliferation and also they show different phenotypes, metastasis patterns and therapeutic response. Studies on genetic heterogeneity of cancer can shed light into the transformation of normal cells to tumour to metastatic clones. A better understanding of tumour heterogeneity can help surpass the barriers to cure different kinds of cancer. The advancements in the field of cancer genomics have churned out a lot of data, which can help in process of unravelling the tumour heterogeneity in cancer.

The aim of the study is to assess the genetic factors and mechanisms, which involve in intra tumour heterogeneity and also how these factors affect clinical outcomes of the patients.  One of the genetic factors we analysed is miRNAs, are involved in wide range of cellular processes like development, differentiation and metabolism, play important role in cancer. Other genetic factors assessed are mutational profiles, copy number variations and altered pathways, and their role in genetic heterogeneity.

In the present projects, we have identified two novel miRNAs, which are over-expressed in breast cancer. Also these two miRs, had implications to the survival of breast cancer patients treated with epirubicin and paclitaxel.  In metastatic malignant melanoma, we have found most metastases within patients to share the majority of mutations, indicating origin from the same subclone in the primary tumour. Mutational signature analysis on the melanoma samples revealed signatures for UV-induced DNA damage, which was expected as the bulk of the mutations in melanoma is caused by UV radiations from sun. Further we have found the level of genomic complexity to be associated with survival in melanoma patients.