内容紹介
Molecular Diagnosis and Treatment of HBOC Syndrome
Summary
Hereditary breast and ovarian cancer(HBOC)is an inherited cancer caused by mutations of the BRCA1 or BRCA2 genes. BRCA genetic testing is used for HBOC diagnosis and continues to progress such as the annotation of VUS. In HBOC clinical practice, surveillance methods have been established through collaboration between genetic medicine and cancer medicine, and treatment, including options based on genetic diagnosis, has advanced significantly. Furthermore, the analysis of BRCA1 and BRCA2 function has progressed, and a novel therapeutic method based on synthetic lethality, such as a PARP inhibitor use, has been developed. Furthermore, BRCA genetic testing is going to be used as a PGx test for the selection of sensitive cases. Meanwhile, familial breast cancer and ovarian cancer, in which cases of breast and ovarian cancer accumulate in the family, vary from some patients carrying a single mutated gene, such as BRCA1, to families that have multifactorial predisposing causes. Responsible genes of each group have been identified as high, moderate, and low susceptibility genes, and there are a number of cases where the responsible genes are unknown. Such genes need to be identified and a new diagnostic system needs to be established.
要旨
遺伝性乳がん・卵巣がん症候群(HBOC)は,BRCA1,BRCA2遺伝子の変異によって発生する遺伝性腫瘍である。BRCA遺伝子検査はHBOC診断の遺伝子検査として始まり,VUS頻度の低下など進歩を続けている。また,HBOC診療においては遺伝診療とがん診療の連携によりサーベイランス法が構築され,BRCA遺伝子診断に基づく治療法の選択肢が増えるなど大きな進展を認めている。さらに,BRCA1,BRCA2機能の解析が進み,PARP阻害剤など合成致死理論に基づく新規治療法が開発され,BRCA遺伝子検査が薬剤選択のPGx検査として使用されようとしている。一方,家系内に乳がんまたは卵巣がんが集積する家族性乳がんや卵巣がんは,HBOCのように単一遺伝子により発症するものから多因子によるものまで多様で,それぞれの原因遺伝子が高度・中等度・低度浸透性遺伝子として同定され,さらに原因遺伝子が不明な症例が少なからず存在し,それらの解明と新たな診療体制の構築が求められている。
目次
Summary
Hereditary breast and ovarian cancer(HBOC)is an inherited cancer caused by mutations of the BRCA1 or BRCA2 genes. BRCA genetic testing is used for HBOC diagnosis and continues to progress such as the annotation of VUS. In HBOC clinical practice, surveillance methods have been established through collaboration between genetic medicine and cancer medicine, and treatment, including options based on genetic diagnosis, has advanced significantly. Furthermore, the analysis of BRCA1 and BRCA2 function has progressed, and a novel therapeutic method based on synthetic lethality, such as a PARP inhibitor use, has been developed. Furthermore, BRCA genetic testing is going to be used as a PGx test for the selection of sensitive cases. Meanwhile, familial breast cancer and ovarian cancer, in which cases of breast and ovarian cancer accumulate in the family, vary from some patients carrying a single mutated gene, such as BRCA1, to families that have multifactorial predisposing causes. Responsible genes of each group have been identified as high, moderate, and low susceptibility genes, and there are a number of cases where the responsible genes are unknown. Such genes need to be identified and a new diagnostic system needs to be established.
要旨
遺伝性乳がん・卵巣がん症候群(HBOC)は,BRCA1,BRCA2遺伝子の変異によって発生する遺伝性腫瘍である。BRCA遺伝子検査はHBOC診断の遺伝子検査として始まり,VUS頻度の低下など進歩を続けている。また,HBOC診療においては遺伝診療とがん診療の連携によりサーベイランス法が構築され,BRCA遺伝子診断に基づく治療法の選択肢が増えるなど大きな進展を認めている。さらに,BRCA1,BRCA2機能の解析が進み,PARP阻害剤など合成致死理論に基づく新規治療法が開発され,BRCA遺伝子検査が薬剤選択のPGx検査として使用されようとしている。一方,家系内に乳がんまたは卵巣がんが集積する家族性乳がんや卵巣がんは,HBOCのように単一遺伝子により発症するものから多因子によるものまで多様で,それぞれの原因遺伝子が高度・中等度・低度浸透性遺伝子として同定され,さらに原因遺伝子が不明な症例が少なからず存在し,それらの解明と新たな診療体制の構築が求められている。