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1. Gene expression signature predicts relapse in adult patients with cytogenetically normal acute myeloid leukemia

Author

Walker, Christopher J., Mrózek, Krzysztof, Ozer, Hatice Gulcin, Nicolet, Deedra, Kohlschmidt, Jessica, Papaioannou, Dimitrios, Genutis, Luke K., Bill, Marius, Powell, Bayard L., Uy, Geoffrey L., Kolitz, Jonathan E., Carroll, Andrew J., Stone, Richard M., Garzon, Ramiro, Byrd, John C., Eisfeld, Ann-Kathrin, de la Chapelle, Albert, and Bloomfield, Clara D.

Published
2021
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2. Genome-wide association study identifies an acute myeloid leukemia susceptibility locus near BICRA

Author

Walker, Christopher J., Oakes, Christopher C., Genutis, Luke K., Giacopelli, Brian, Liyanarachchi, Sandya, Nicolet, Deedra, Eisfeld, Ann-Kathrin, Scholz, Markus, Brock, Pamela, Kohlschmidt, Jessica, Mrózek, Krzysztof, Bill, Marius, Carroll, Andrew J., Kolitz, Jonathan E., Powell, Bayard L., Wang, Eunice S., Niederwieser, Dietger W., Stone, Richard M., Byrd, John C., Schwind, Sebastian, de la Chapelle, Albert, and Bloomfield, Clara D.

Published
2019
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5. Distinct Gene Expression Profiles and Mutations Associate with Outcome in Younger Adults with De Novo Cytogenetically Normal Acute Myeloid Leukemia (CN-AML) (Alliance)

Author

Walker, Christopher J., primary, Eisfeld, Ann-Kathrin, additional, Ozer, Hatice G, additional, Kohlschmidt, Jessica, additional, Nicolet, Deedra, additional, Mrózek, Krzysztof, additional, Papaioannou, Dimitrios, additional, Genutis, Luke K, additional, Powell, Bayard L, additional, Uy, Geoffrey L., additional, Kolitz, Jonathan E., additional, Carroll, Andrew J., additional, Stone, Richard, additional, Garzon, Ramiro, additional, Byrd, John C., additional, de la Chapelle, Albert, additional, and Bloomfield, Clara D., additional

Published
2019
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6. Genetic Characterization and Prognostic Relevance of Acquired Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia

Author

Walker, Christopher J., primary, Kohlschmidt, Jessica, additional, Eisfeld, Ann-Kathrin, additional, Mrózek, Krzysztof, additional, Liyanarachchi, Sandya, additional, Song, Chi, additional, Nicolet, Deedra, additional, Blachly, James S., additional, Bill, Marius, additional, Papaioannou, Dimitrios, additional, Oakes, Christopher C., additional, Giacopelli, Brian, additional, Genutis, Luke K., additional, Maharry, Sophia E., additional, Orwick, Shelley, additional, Archer, Kellie J., additional, Powell, Bayard L., additional, Kolitz, Jonathan E., additional, Uy, Geoffrey L., additional, Wang, Eunice S., additional, Carroll, Andrew J., additional, Stone, Richard M., additional, Byrd, John C., additional, de la Chapelle, Albert, additional, and Bloomfield, Clara D., additional

Published
2019
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7. Mutations in Genes Associated with Familial Predisposition to Myeloid Neoplasms: Their Frequency and Associations with Pretreatment Characteristics in Adult Patients (Pts) with Presumably Sporadic De Novo Acute Myeloid Leukemia (AML)

Author

Eisfeld, Ann-Kathrin, primary, Kohlschmidt, Jessica, additional, Mrózek, Krzysztof, additional, Mims, Alice S., additional, Walker, Christopher J., additional, Nicolet, Deedra, additional, Blachly, James S., additional, Genutis, Luke K, additional, Carroll, Andrew J., additional, Powell, Bayard L., additional, Kolitz, Jonathan E., additional, Stone, Richard M., additional, de la Chapelle, Albert, additional, Byrd, John C., additional, and Bloomfield, Clara D., additional

Published
2018
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8. Genome-Wide Association Study (GWAS) Identifies a Significant Acute Myeloid Leukemia (AML) Susceptibility Locus Near BICRA

Author

Walker, Christopher J., primary, Oakes, Christopher C., additional, Genutis, Luke K, additional, Giacopelli, Brian, additional, Liyanarachchi, Sandya, additional, Nicolet, Deedra, additional, Eisfeld, Ann-Kathrin, additional, Scholz, Markus, additional, Brock, Pamela, additional, Kohlschmidt, Jessica, additional, Mrózek, Krzysztof, additional, Bill, Marius, additional, Carroll, Andrew J., additional, Kolitz, Jonathan E., additional, Powell, Bayard L., additional, Wang, Eunice S., additional, Niederwieser, Dietger, additional, Stone, Richard M., additional, Byrd, John C., additional, Schwind, Sebastian, additional, de la Chapelle, Albert, additional, and Bloomfield, Clara D., additional

Published
2018
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9. Genome-wide association study identifies an acute myeloid leukemia susceptibility locus near BICRA

Author

Walker, Christopher J., primary, Oakes, Christopher C., additional, Genutis, Luke K., additional, Giacopelli, Brian, additional, Liyanarachchi, Sandya, additional, Nicolet, Deedra, additional, Eisfeld, Ann-Kathrin, additional, Scholz, Markus, additional, Brock, Pamela, additional, Kohlschmidt, Jessica, additional, Mrózek, Krzysztof, additional, Bill, Marius, additional, Carroll, Andrew J., additional, Kolitz, Jonathan E., additional, Powell, Bayard L., additional, Wang, Eunice S., additional, Niederwieser, Dietger W., additional, Stone, Richard M., additional, Byrd, John C., additional, Schwind, Sebastian, additional, de la Chapelle, Albert, additional, and Bloomfield, Clara D., additional

Published
2018
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10. The Role of NRG1 in the Predisposition to Papillary Thyroid Carcinoma

Author

He, Huiling, primary, Li, Wei, additional, Liyanarachchi, Sandya, additional, Wang, Yanqiang, additional, Yu, Lianbo, additional, Genutis, Luke K, additional, Maharry, Sophia, additional, Phay, John E, additional, Shen, Rulong, additional, Brock, Pamela, additional, and de la Chapelle, Albert, additional

Published
2017
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11. Variants in microRNA genes in familial papillary thyroid carcinoma

Author

Tomsic, Jerneja, primary, Fultz, Rebecca, additional, Liyanarachchi, Sandya, additional, Genutis, Luke K., additional, Wang, Yanqiang, additional, Li, Wei, additional, Volinia, Stefano, additional, Jazdzewski, Krystian, additional, He, Huiling, additional, Wakely, Paul E, additional, Senter, Leigha, additional, and de la Chapelle, Albert, additional

Published
2016
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12. Variants in LRRC34reveal distinct mechanisms for predisposition to papillary thyroid carcinoma

Author

Comiskey Jr., Daniel Forrest, He, Huiling, Liyanarachchi, Sandya, Sheikh, Mehek S, Genutis, Luke K, Hendrickson, Isabella V, Yu, Lianbo, Brock, Pamela L, and de la Chapelle, Albert

Abstract

BackgroundPapillary thyroid carcinoma (PTC) demonstrates high heritability and a low somatic mutation burden relative to other cancers. Therefore, the genetic risk predisposing to PTC is likely due to a combination of low penetrance variants. A recent genome-wide association study revealed the association of PTC with a missense variant, rs6793295, at 3q26 in a gene called Leucine Repeat Rich Containing 34 (LRRC34).MethodsWe report the mechanisms of PTC risk at 3q26 using a combination of overexpression, mass spectroscopy, knockdown, transcriptome profiling, migration assays and genetic analysis.ResultsWe observed differential binding of wild-type and missense LRRC34 to RANBP1. Overexpression of missense LRRC34 reduced RanGTP levels and increased apoptosis. We also identified a second linkage disequilibrium (LD) block upstream of LRRC34containing regulatory variants with allele-specific expression. Transcriptome profiling of LRRC34knockdown cells showed changes in genes involved with cellular movement. LRRC34knockdown reduced the migration of thyroid cancer cell lines. Lastly, we assessed the relative contribution of PTC risk from each locus using haplotype analysis.ConclusionsOur study demonstrates two separate mechanisms, one in G protein signalling and the other in transcriptional control, dictating PTC risk at 3q26 using both biochemical and genetic techniques.

Published
2020
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13. The Role of NRG1 in the Predisposition to Papillary Thyroid Carcinoma.

Author

He, Huiling, Li, Wei, Liyanarachchi, Sandya, Wang, Yanqiang, Yu, Lianbo, Genutis, Luke K, Maharry, Sophia, Phay, John E, Shen, Rulong, Brock, Pamela, and de la Chapelle, Albert

Abstract

Previous genome-wide association studies have shown that single-nucleotide polymorphism (SNP) rs2439302 in chromosome 8p12 is significantly associated with papillary thyroid carcinoma (PTC) risk and dysregulated NRG1 expression. The underlying mechanisms remain to be discovered.

Published
2018
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14. Distinct Gene Expression Profiles and Mutations Associate with Outcome in Younger Adults with De NovoCytogenetically Normal Acute Myeloid Leukemia (CN-AML) (Alliance)

Author

Walker, Christopher J., Eisfeld, Ann-Kathrin, Ozer, Hatice G, Kohlschmidt, Jessica, Nicolet, Deedra, Mrózek, Krzysztof, Papaioannou, Dimitrios, Genutis, Luke K, Powell, Bayard L, Uy, Geoffrey L., Kolitz, Jonathan E., Carroll, Andrew J., Stone, Richard, Garzon, Ramiro, Byrd, John C., de la Chapelle, Albert, and Bloomfield, Clara D.

Abstract

Approximately 20% of CN-AML patients (pts) younger than 60 years treated with current standard intensive combination chemotherapy regimens have primary refractory disease, and among pts who achieve a complete remission (CR), over half relapse. Thus, early detection of pts with low likelihood of achieving a CR and those with a high likelihood of relapsing is of crucial importance.

Published
2019
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15. Variants in microRNA genes in familial papillary thyroid carcinoma.

Author

Tomsic J, Fultz R, Liyanarachchi S, Genutis LK, Wang Y, Li W, Volinia S, Jazdzewski K, He H, Wakely PE Jr, Senter L, and de la Chapelle A

Subjects
Animals, Biomarkers, Tumor metabolism, COS Cells, Carcinoma, Papillary metabolism, Carcinoma, Papillary pathology, Chlorocebus aethiops, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, HEK293 Cells, Heredity, Humans, MicroRNAs metabolism, Pedigree, Phenotype, Risk Factors, Sequence Analysis, RNA, Thyroid Cancer, Papillary, Thyroid Neoplasms metabolism, Thyroid Neoplasms pathology, Transfection, Biomarkers, Tumor genetics, Carcinoma, Papillary genetics, Genetic Variation, MicroRNAs genetics, Thyroid Neoplasms genetics
Abstract

Papillary Thyroid Carcinoma (PTC) displays one of the highest familiality scores of all cancers as measured by case-control studies, yet only a handful of genes have been implicated until now. Variants in microRNAs have been associated with the risk of several cancers including PTC but the magnitude of this involvement is unclear. This study was designed to test to what extent genomic variants in microRNAs contribute to PTC risk. We used SOLiD technology to sequence 321 genomic regions encoding 427 miRNAs in one affected individual from each of 80 PTC families. After excluding variants with frequency ≥ 1% in 1000 Genomes Phase 1 (n = 1092) we detected 1978 variants. After further functional filtering steps 25 variants in pre-miRs remained. Co-segregation was observed for six out of 16 tested miRNA variants with PTC in the families, namely let-7e, miR-181b, miR-135a, miR-15b, miR-320, and miR-484. Expression of miR-135a and miR-181b was tested in normal thyroid and tumor tissue from patients that carry the variants and a decrease in expression was observed. In vitro assays were applied to measure the effect of the variants on microRNAs' maturation. Four out of six variants were tested. Only the let-7e and miR-181b variants showed an effect on processing leading to lower levels of mature miRNA. These two variants were not detected in 1170 sporadic PTC cases nor in 1404 controls. Taken together, our data show that high penetrance germline sequence variants of miRNAs potentially predispose to a fraction of all PTC but are not common.

Published
2017
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