Question

It has been noted that breast cancer tumor biopsies appear to contain a heterogenous population of cells.

a. Describe two ways (briefly) that you can show that there indeed is a heterogenous population of cells

b. Do you think the different cells have differing potential to generate tumors and if so how can you definitively show this?

Answer 1

Answer-Tumor heterogeneity is undoubtedly due,at least in part to the stability of multiple genomic clonal population within a neoplasm.This arise from divergent evolution of the originating cells progeny and may be sustained by geographical isolation within the tumor and cooperation between clones.Changes in nature and order of early driver mutations can lead to highly divergent evolution between tumors and reinforce the profound intertumor heterogeneity seen in human tumors.Passenger mutation in these population may lead to altered epigenetic attractor states and a burring of boundaries between cellular phenotype.Tumor extrinsic features of the ECM and TME lead to dynamic oscillation between epigenetically regulated phenotypes.Spatial heterogeneity in TME components across a tumor may reinforce intra tumor heterogeneity whereas global changes in TME between patients influences intra tumor heterogeneity.the CSC theory of tumor initiation and progression posits that cancer follows the same principle as embryogenesis and normal tissue renewal.A more direct measure of tumor heterogeneity is the cancer cell fraction,which is the fraction of cells having a specific SNV .We determined the CCF's for all cancer and multicellular cells using Pyclone ,and calculated MATH score using CCF's instead of allele frequency. Answer-Yes,different cells have different potential to generate tumor.If tumor cells start replicating they don't behave like normal cells .They don't know when to stop replicating and when to die.they don't always stick together ,so they might break away and move through the blood vessels or lymphatic system and start growing somewhere else in the body.This process is known as metastasis.Tumors start to create their own blood vessels so that they can continue to grow .The blood vessels supply they with extra oxygen ,glucose and hormones.this is called angiogenesis.Once a tumor does this it can start to invade the surrounding tissue.This active tumor cells can enter blood and lymphatic system and travel to other parts and start the process of tumor all over again.