As I understand it, the goal of every Buddhist is to reach enlightenment, to “awaken” (although they probably would not like to call that a “goal”). So, I would say that the primary Buddhist hypothesis is that we can reach enlightenment, that we can awaken, which one Buddhist scholar considers to be “the supreme attainment, capable of eliminating all your suffering and fears, reaching the refuge of peace” (http://www.accesstoinsight.org/lib/thai/lee/refawake.html).
And the other key hypotheses are in the Four Noble Truths. I think the first one (there is suffering/stress) is pretty obvious. But already the second one is not all encompassing, imho: “the cause of this stress is our self-centered craving for life to be otherwise” (http://www.dharmapunxnyc.com/basics.html). What does science have to say about that? I agree that we can add to our stress with our thinking but I don’t think that’s all there is.
(As far as I can tell, the quotes are from Theravada Buddhists, who claim to practice most closely in accordance to the Buddha’s teachings).