Coming to Grey's Anatomy: New Hookup, Devastating Breakup

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Brace yourself, Grey's Anatomy fans.

According to inside sources, there's a major shakeup coming by the end of this season - one that will result in a Seattle Grace couple calling it quits. But this is heavier than usual.

Apparently, it's "one of the longer-term, most-loved couples" that splits up, and it's "going to leave both of them pretty devastated." Doesn't sound good, does it? There's more still.

The backdrop of the breakup involves "a very serious issue "that it certainly seems like the two cannot get past - and does not arise because either of them have met someone new.

Any guesses?

Gather 'Round

Everybody's going to be glued to Grey's Anatomy message boards after this.

Meanwhile, there's also going to be a new fling in the hospital we love, and it involves one of the newcomers this season, and someone who's been around for a good long while. 

One clue to the hookup: It stinks (and only die-hard fans of a certain other show will get that reference)! If you have any theories on this, we'd welcome them in the comments.

Finally, we hear that the Grey's Anatomy sixth season finale will be "a serious game changer for every single character." Okay, Shonda Rhimes said that, but it's worth repeating.

Sound off below with who you think the breakup - and hookup - involves, and what you think the upcoming season-ending Grey's Anatomy bonanza will entail ...

Steve Marsi is the Managing Editor of TV Fanatic. Follow him on Google+ or email him here.

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Grey's Anatomy Quotes

Arizona: Oh my God! I mean, I understand why you're into her. She's hot. Wait, she likes you?
Nathan: What? I mean, I'm going to try not to be offended at that.
Arizona: No, no, no. It's just that Derek was--Derek was epic for her. They were the great love story. I mean, that girl's heart beat for Derek Shepherd. It never occurred to me that she would ever be with anyone else. He was perfect. He was everything. That man turned her world. It...I spooked you. Don't be spooked.

MEREDITH: "You don't get to call me a whore. When I met you, I thought I had found the person that I was going to spend the rest of my life with. I was done! All the boys and all the bars and all the obvious daddy issues, who cares? I was done. You left me. You chose Addison. I'm all glued back together now. I make no apologies for how I chose to repair what you broke. You don't get to call me a whore."
DEREK: "This thing with us is finished. It's over."
MEREDITH: "Finally."
DEREK: "Yeah, it's done."
MEREDITH: "It is done."