Clonal Expansion,”explains overwhelming majority of cancersinitial single event happens w/ initial mutation which allows one cell in all cohorts to have proliferative damagecould be loss of tumor suppressor (eliminate DNA damage checkpoints, other DNA mutations can occur)cell not going to proliferate all of its progenetersGoing to get a population of cells that expand and harbor the initial mutation (proliferating) and going through DNA replicationIf they acquire subsequent mutation, that can also be selectedA type of second mutation that you can select for here might be mutation that allows cancer cell to escape immune surveillance (cells now have selective advantage)out of initial population, now have cohort of cellsmall # of cells now requires 2nd mutation, now acquiring 3rd mutationdeprived of oxygen; altered metabolism (cells basically have Raf and Ras mutations have increased GLUT1 transporters, able to import glucose more readily)Looking at 100s of mutations, and comparing DNA sequence of normal cell, and all cells in intermediate states in progression
and see that genetic signature is constantly changing”