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Former President Bill Clinton and Senator Hillary Rodham Clinton said Reeve was "a model of tenacity and grace".
"Despite the adversity that she faced, Dana bravely met these challenges and was always an extremely devoted wife, mother and advocate. Dana was an inspiration to us and we will miss her," the Clintons said.
The Reeves' 13-year-old son Will is living with family friends.
Will Reeve has been orphaned less than 18 months after his father's death.
Tributes to Dana Reeve poured in from the celebrities who met her as she and her paralysed husband fought for more money for stem-cell research.
"The brightest light has gone out," said comedian Robin Williams, who delivered the eulogy at Christopher Reeve's funeral.
"We will forever celebrate her loving spirit."
Actress Catherine Zeta Jones, a supporter of the foundation, said of Reeve recently: "She's better than Superwoman, she's Wonder Woman. Dana is like a saint to me."
"We are extremely saddened by the death of Dana Reeve, whose grace and courage under the most difficult of circumstances was a source of comfort and inspiration to all of us," Ms Kathy Lewis said in a statement.
In 2005, Dana's mother died of complications from ovarian cancer.
Dana's lung cancer was diagnosed last August and initial treatments had appeared to be successful.
She sang on stage at Madison Square Garden in January, but was soon readmitted to a New York hospital.
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