CHEK2 (checkpoint kinase 2; MIM# 604373) is a tumor suppressor gene that encodes a serine threonine kinase involved in pathways such as DNA repair, cell cycle arrest, mitosis, and apoptosis. Pathogenic variants in CHEK2 contribute to a moderately increased risk of breast and other cancers. Several variant classes have been reported, either point mutations or large intragenic rearrangements. However, a significant portion of reported variants has an uncertain clinical significance. We report an intragenic CHEK2 duplication, ranging from intron 5 to intron 13, identified in an Italian family with hereditary breast cancer. Using long range PCR, with duplication-specific primers, we were able to ascertain the genomic breakpoint. We also performed a real-time PCR to assess a possible loss-of-function effect. The genomic characterization of large intragenic rearrangements in cancer susceptibility genes is important for the clinical management of the carriers and for a better classification of rare variants. The molecular definition of breakpoints allows for the prediction of the impact of the variant on transcripts and proteins, aiding in its characterization and clinical classification.

Genomic Breakpoints’ Characterization of a Large CHEK2 Duplication in an Italian Family with Hereditary Breast Cancer / Germani, Aldo; Guadagnolo, Daniele; Salvati, Valentina; Micolonghi, Caterina; Mancini, Rita; Mastromoro, Gioia; Sadeghi, Soha; Petrucci, Simona; Pizzuti, Antonio; Piane, Maria. - In: DIAGNOSTICS. - ISSN 2075-4418. - 12:7(2022), pp. 1-13. [10.3390/diagnostics12071520]

Genomic Breakpoints’ Characterization of a Large CHEK2 Duplication in an Italian Family with Hereditary Breast Cancer

Germani, Aldo;Guadagnolo, Daniele
;
Salvati, Valentina;Micolonghi, Caterina;Mastromoro, Gioia;Sadeghi, Soha;Petrucci, Simona;Pizzuti, Antonio;Piane, Maria
2022

Abstract

CHEK2 (checkpoint kinase 2; MIM# 604373) is a tumor suppressor gene that encodes a serine threonine kinase involved in pathways such as DNA repair, cell cycle arrest, mitosis, and apoptosis. Pathogenic variants in CHEK2 contribute to a moderately increased risk of breast and other cancers. Several variant classes have been reported, either point mutations or large intragenic rearrangements. However, a significant portion of reported variants has an uncertain clinical significance. We report an intragenic CHEK2 duplication, ranging from intron 5 to intron 13, identified in an Italian family with hereditary breast cancer. Using long range PCR, with duplication-specific primers, we were able to ascertain the genomic breakpoint. We also performed a real-time PCR to assess a possible loss-of-function effect. The genomic characterization of large intragenic rearrangements in cancer susceptibility genes is important for the clinical management of the carriers and for a better classification of rare variants. The molecular definition of breakpoints allows for the prediction of the impact of the variant on transcripts and proteins, aiding in its characterization and clinical classification.
2022
chek2; hereditary breast cancer; intragenic duplication; large rearrangement
01 Pubblicazione su rivista::01i Case report
Genomic Breakpoints’ Characterization of a Large CHEK2 Duplication in an Italian Family with Hereditary Breast Cancer / Germani, Aldo; Guadagnolo, Daniele; Salvati, Valentina; Micolonghi, Caterina; Mancini, Rita; Mastromoro, Gioia; Sadeghi, Soha; Petrucci, Simona; Pizzuti, Antonio; Piane, Maria. - In: DIAGNOSTICS. - ISSN 2075-4418. - 12:7(2022), pp. 1-13. [10.3390/diagnostics12071520]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1649089
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