At various times in my life I've heard about great things that have been lost to the world, and to the world of literature in particular. Wouldn't that make a cool idea for a mystery - with the main character on the trail of something that vanished years ago but then turns up, perhaps in nefarious hands?
As a rule I don't care for mysteries, but I can't quite imagine this as any other genre. What comes naturally seems to be a sort of really intelligent Indiana Jones story. "Intelligent," in this case, meaning "geeky."
Perhaps the nascent genius who will take up this idea and run with it will have other ideas how to write about cool stuff that's tragically disappeared over the years . . . such as:
1. The Library of Alexandria: The library was founded sometime during the 3rd century BCE and partially burned at various junctures before it was finally destroyed (by Christians) in 391 CE. It was THE repository for ancient texts, probably mostly Greek. Think of it in terms of: all the fabulous ancient poems, plays, and other writings that we have today are merely what survived the destruction of the library.
I heard someone suggest once that the scrolls that were saved were only saved because they were outside the library on the "sale" table that day, and all the "good stuff" was inside. Now that's something to think about. How cool would it be if some of those texts turned up!
2. Hemingway's early drafts: All of Ernest Hemingway's early work (drafts and carbon copies) was packed in a suitcase, which was stolen and never recovered. Whether those early stories were any good is the subject of much conjecture, but if they ever turned up, they would be a fantastic literary and historical record and a rich treasure for scholars. And perhaps first wife Hadley, who took the blame for the loss, could be vindicated, too, somehow. (At least one author has used this material, but surely there is room for other interpretations.)