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Conclusion:
The present data show that CUP is not a disease of random metastatic cancers but, instead, a disease of a defined set of cancers. The association of CUP with families of kidney, lung, and colorectal cancers suggests a marked genetic basis and shared metastatic mechanisms by many cancer types. Familial sites shared by CUP generally match those arising in tissue-of-origin determinations and, hence, suggest sites of origin for CUP. Mechanistic exploration of CUP may provide insight into defense against primary tumors and the metastatic process.
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