Key Points We observed that SMAD7, a negative regulator of TGF-β receptor-I kinase, is markedly reduced in MDS, and leads to ineffective hematopoiesis. Increased levels of microRNA-21 are seen in MDS and reduce SMAD7 levels, thus overactivating TGF-β signaling.

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e22196 Background: Recurring polysomies in diverse tumors at different times may suggest common neoplastic mechanisms. Following case demonstrates similar polysomies in breast, endometrial and cholangiocarcinoma arising at different times. Methods: A 79-year-old African American female was diagnosed poorly differentiated cholangiocarcinoma. Tumor markers (CEA, AFP, CA19-9) were normal. FISH analysis with D3Z1 (centromere 3), D7Z1 (centromere 7), CDKN2A (9p21) and D17Z1 (centromere 17) DNA probes (Abbott Molecular, IL. USA) revealed polysomy of chromosomes 3, 7, 9 and 17. Oncology history includes tumors noted in the table. Medical history includes aortic aneurysm, hypertension, IPF, obesity, CKD, DJD, cholecystectomy and adjuvant tamoxifen. She was never pregnant, non smoker non alcoholic and no prior chemical exposures. Her maternal aunt had unclear pelvic cancer at 70. Her niece had duodenal cancer in 40s. Possible common initiating neoplastic mechanism or predisposition was speculated in view of multiple tumors. Archived specimens of previous tumors were tested using the same FISH probe set. Results: Similar pattern of aneuploidy was noted in cholandiocarcinoma, DCIS and endometrial polyp specimen and no such abnormalities in parathyroid adenoma and in normal tissue. Conclusions: Occurrences of similar polysomy in tumors originating from diverse tissues at different times but not in normal tissue suggest common predisposition and/or similar, nonrandom, neoplastic molecular events. Uncommon and previously not described polysomy pattern was noted in DCIS and in endometrial polyp. [Table: see text]