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Sock Hoai Chan and Joanne Ngeow

). Hereditary cancers, or cancer-predisposing syndromes, are associated with inherited germline mutations that increase an individual’s lifetime risk of cancer ( Garber & Offit 2005 ). One example is the hereditary non-polyposis colon cancer (HNPCC), also known

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Yulong Li, Jianhua Zhang, Poorni R Adikaram, James Welch, Bin Guan, Lee S Weinstein, Haobin Chen, and William F Simonds

-stage diagnosis and increased chance of cure. CDC73 , formerly known as HRPT2 , is a key gene implicated in development of parathyroid cancer. It is a putative tumor suppressor gene with 17 exons ( Fig. 1 ), and multiple germline and somatic mutations have been

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Jan P Dumanski, Chiara Rasi, Peyman Björklund, Hanna Davies, Abir S Ali, Malin Grönberg, Staffan Welin, Halfdan Sorbye, Henning Grønbæk, Janet L Cunningham, Lars A Forsberg, Lars Lind, Erik Ingelsson, Peter Stålberg, Per Hellman, and Eva Tiensuu Janson

al . 2001 , Pal et al . 2001 , Jarhult et al . 2010 , Cunningham et al . 2011 , Sei et al . 2015 ). Furthermore, we hypothesized that germline mutations (studied via analyses of blood DNA), that might be identified in familial subjects, should

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Yuji Ikeda, Kazuma Kiyotani, Poh Yin Yew, Taigo Kato, Kenji Tamura, Kai Lee Yap, Sarah M Nielsen, Jessica L Mester, Charis Eng, Yusuke Nakamura, and Raymon H Grogan

breast ( Eng 1993 ). PTEN is one of the causative genes of CS or Cowden-like syndrome (CLS) ( Liaw et al . 1997 ), and germline mutations are found in 25–85% of CS patients and <5% of CLS patients ( Marsh et al . 1998 , Tan et al . 2011 ). Germline

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Daniela Cordella, Marina Muzza, Luisella Alberti, Paolo Colombo, Pietro Travaglini, Paolo Beck-Peccoz, Laura Fugazzola, and Luca Persani

-oncogene have been associated with several inherited and non-inherited diseases. Inactivating mutations cause familial and sporadic Hirschsprung disease (OMIM*142623), a syndrome of congenital absence of enteric innervation ( Romeo et al. 1994 ). Germline

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F Cetani, E Pardi, E Ambrogini, P Viacava, S Borsari, M Lemmi, L Cianferotti, P Miccoli, A Pinchera, A Arnold, and C Marcocci

with sporadic PHPT, who had two recurrences after successful surgery over a 17-year follow-up. This unusual history prompted us to perform genetic studies, which led to the identification of a HRPT2 germline mutation associated with independent HRPT2

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Maria Grazia Borrello, Antonella Aiello, Bernard Peissel, Maria Grazia Rizzetti, Piera Mondellini, Debora Degl'Innocenti, Veronica Catalano, Morena Gobbo, Paola Collini, Italia Bongarzone, Marco A Pierotti, Angela Greco, and Ettore Seregni

-of-function alterations. Somatic rearrangements of RET are present in about one-third of papillary thyroid carcinomas (reviewed in Greco et al . (2009) ), whereas specific germline activating mutations of RET are causally involved in hereditary medullary thyroid

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Yilun Deng, Shahida K Flores, ZiMing Cheng, Yuejuan Qin, Robin C Schwartz, Carl Malchoff, and Patricia L M Dahia

Dear Editor, Germline mutations of the endomembrane-encoding gene TMEM127 confer susceptibility to neural crest-derived tumors pheochromocytomas (PHEOs) ( Qin et al . 2010 ), and have also been found in isolated renal cell carcinomas (RCCs

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Bora E Baysal and Eamonn R Maher

(tumors were only manifest after paternal transmission, Fig. 1 ) was reported ( van der Mey et al . 1989 ). Ten years later, Baysal et al . (2000) reported the seminal finding that familial HNPGL was associated with germline mutations in succinate

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Esther Korpershoek, Bart-Jeroen Petri, Francien H van Nederveen, Winand N M Dinjens, Albert A Verhofstad, Wouter W de Herder, Sonja Schmid, Aurel Perren, Paul Komminoth, and Ronald R de Krijger

germline mutations of the RET protooncogene, which are mostly (80–96%) found in RET exons 10, 11, and 16 ( Thakker 2001 , Peczkowska & Januszewicz 2005 ). Somatic RET mutations have also been found in sporadic PCC affecting exons 10, 11, and 16