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Background. Familial Papillary Thyroid Carcinoma (PTC) has been recently associated with the HABP2 p.G534E mutation. In this study we evaluated the putative association of the HABP2 p.G534E mutation and familial history of PTC and Breast Carcinoma (BC) in the Brazilian population. Methods. Germline mutations of twenty unrelated individuals with personal and/or family history of PTC and/or BC were identified by whole exome sequencing (WES), using Nextera Exome Enrichment kit and HiSeq200 platform (Illumina). Two cases were positive for p.G534E. Family members from both positive cases (seven from Family 1 and three from Family 2) were recruited for segregation analysis. An additional patient and three relatives (Family 3) with history of PTC and BC were included for validation. Fifty frozen PTC tumor samples and 170 healthy Brazilian individuals were also screened for the HABP2 variant. Confirmation and validation were performed by Sanger sequencing. Results. Interestingly, Family 1 reported a consanguineous history, reflected in two homozygous cases: the proband (PTC) and his unaffected sister. Also, only one (BC) out of eight tested members was negative for p.G534E. In the Family 2, the only patient diagnosed with PTC was negative for the mutation, while three relatives were positive for the same loci. The index case (PTC) from Family 3, was wild type for HABP2 and three relatives tested were positive carriers. In PTC tumor samples the Allele Frequency (AF) was 0.04: two heterozygous and one homozygous for p.G534E. Among 170 healthy individuals, five were heterozygous for the variant, representing an AF of 0.0147. The two index patients evaluated by WES also presented interesting pathogenic variants in genes potentially associated with deregulation of the extracellular matrix organization pathway (CTSB, TNXB, COL4A3, COL16A1, COL24A1, COL5A2, NID1, LOXL2, MMP11, TRIM24 and MUSK) and DNA repair function (NBN and MSH2). Conclusion. Our findings suggest that HABP2 is not a predisposition gene involved in familial PTC and BC. Financial Support: FAPESP (2013/01867-8 and 2014/03983-8) and CNPq (481132/2012-0) Note: This abstract was not presented at the meeting. Citation Format: Maisa Pinheiro, Sandra A. Drigo, Fabio A. Marchi, Renata Tonhosolo, Sonia C. Andrade, Igor Jurisica, Luiz P. Kowalski, Maria Isabel W. Achatz, Silvia R. Rogatto. HABP2 p.G534E variant in patients with family history of thyroid and breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4287. doi:10.1158/1538-7445.AM2017-4287

A significant number of patients with family history of breast (BC) and papillary thyroid carcinomas (PTC) have been detected at Oncogenetics Dept of AC Camargo Cancer Center, SP, Brazil. The aim of this study was to identify genetic alterations in patients with family cancer history of BC and TC by using whole exome sequencing (WES) analysis. All patients included in this study fulfilled the inclusion criteria as follows: proband with non-medullary TC and/or BC with family cancer history of these tumors AND at least two 1st- or 2nd- degree relatives with one of these tumors either diagnosed Financial Support: FAPESP (2013/01867-8 and 2014/03983-8) and CNPq (481132/2012-0) Citation Format: Maisa Pinheiro, Fabio Marchi, Sandra Drigo, Patricia Reis, Luiz Lehmann Coutinho, Sonia Andrade, Luis Paulo Kowaslki, Maria Isabel Achatz, Silvia Rogatto. Identification of predisposition genes involved in thyroid and breast carcinomas in patients with family history of these tumors by whole exome sequencing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2751. doi:10.1158/1538-7445.AM2015-2751