PGT在遗传性肿瘤生殖干预中的应用进展

doi:10.19401/j.cnki.1007-3639.2022.11.001

中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (11): 1037-1043.doi: 10.19401/j.cnki.1007-3639.2022.11.001

PGT在遗传性肿瘤生殖干预中的应用进展

曹现岭¹^,²(), 周宣佑¹^,², 陈松长¹^,², 黄荷凤¹^,², 徐晨明¹^,²()

1.复旦大学附属妇产科医院妇产科遗传中心，上海 200011
2.复旦大学生殖与发育研究院，上海 200032

收稿日期:2022-10-15 修回日期:2022-11-15 出版日期:2022-11-30 发布日期:2022-12-14
通信作者: 徐晨明
作者简介:曹现岭（ORCID: 0000-0001-9544-7419），博士在读。
徐晨明，博士，研究员，博士研究生导师，复旦大学附属妇产科医院妇产科遗传中心副主任。从事生殖遗传、产前诊断的临床和科研工作20余年，主要研究方向是生殖相关疾病的发病机制研究、植入前胚胎遗传学检测、产前遗传诊断的技术研发和临床转化应用。兼任上海市医学会分子诊断专科分会副主任委员、中国医师协会医学遗传医师分会委员、中国遗传学会遗传诊断分会委员等。主持国家自然科学基金项目5项和上海市科学技术委员会课题4项，作为骨干人员参加国家重大研究计划、国家重点研发计划3项，作为主要完成人获得国家级及省部级奖励多项。近年来在Cell Discovery、Clinical Chemistry、Thyroid等国内外学术刊物上发表论文60余篇，主编和副主编专著各1部，参编专著6部，获国家发明专利4项。

Progress in the application of PGT in hereditary tumors

CAO Xianling¹^,²(), ZHOU Xuanyou¹^,², CHEN Songchang¹^,², HUANG Hefeng¹^,², XU Chenming¹^,²()

1. Genetics Center of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
2. Institute of Reproduction and Development, Fudan University, Shanghai 200032, China

Received:2022-10-15 Revised:2022-11-15 Published:2022-11-30 Online:2022-12-14
Contact: XU Chenming

摘要/Abstract

摘要：

遗传性肿瘤本质上是遗传物质缺陷导致的疾病，大多数呈现出孟德尔常染色体显性遗传规律，不仅危害患者的健康，而且对后代构成严重威胁。遗传性肿瘤胚胎植入前遗传学检测（preimplantation genetic testing，PGT）是利用外受精-胚胎移植（in vitro fertilization and embryo transfer，IVF-ET）和遗传学检测技术，对卵母细胞的极体、第3天的胚胎或第5天的囊胚进行遗传性肿瘤致病基因的检测，选择无遗传性肿瘤易感基因致病性变异的胚胎移植到子宫中，从而阻断遗传性肿瘤的子代传递并降低后代患病风险。本文简要介绍目前常见的遗传性肿瘤及其特征，总结PGT技术在家族性腺瘤性息肉病、遗传性乳腺癌/卵巢癌综合征等常见遗传性肿瘤及罕见遗传性肿瘤生殖干预中的应用，探讨遗传性肿瘤PGT技术的发展和伦理问题，并对其未来发展方向进行展望。

关键词: 遗传性肿瘤, 胚胎植入前遗传学检测, 应用进展

Abstract:

Hereditary tumors are essentially diseases caused by genetic material defects, and most of them exhibit Mendelian autosomal dominant inheritance. It not only endangers the health of patients, but also poses a serious threat to future generations. Preimplantation genetic testing (PGT) combined with in vitro fertilization and embryo transfer (IVF-ET) technology can detect the chromosomes or specific genes of gametes or embryos, and finally select embryos without pathogenic mutations of hereditary tumor susceptibility genes to be implanted into the uterus, thereby blocking the offspring transmission of hereditary tumors and reducing their incidence. This article briefly introduced the common hereditary tumors and their characteristics at present, summarized the application of PGT technology in reproductive intervention of common hereditary tumors and rare hereditary tumors such as familial adenomatous polyposis, hereditary breast cancer/ovarian cancer syndrome, discussed the development and ethical issue of PGT technology for hereditary tumors, and looked forward to its future development direction.

Key words: Hereditary tumors, Preimplantation genetic testing, Application progress

中图分类号:

曹现岭, 周宣佑, 陈松长, 黄荷凤, 徐晨明. PGT在遗传性肿瘤生殖干预中的应用进展[J]. 中国癌症杂志, 2022, 32(11): 1037-1043.

CAO Xianling, ZHOU Xuanyou, CHEN Songchang, HUANG Hefeng, XU Chenming. Progress in the application of PGT in hereditary tumors[J]. China Oncology, 2022, 32(11): 1037-1043.

图/表 1

表1

常见的癌症综合征及其易感基因和表型特征"

Syndrome	Gene	Phenotypic features
HBOC1	BRCA1	Female breast, ovarian and colorectal cancer
HBOC2	BRCA2	Male and female breast, ovarian, prostate and pancreatic cancer
FAP	APC/CHRPE	Multiple colorectal and upper gastrointestinal adenomatous polyps, fibroma, epidermoid cyst
Hereditary non-polyposis colorectal cancer	MLH1, MSH2, MSH6, PMS2, PMS1	Colorectal, endometrial, ovarian, gastric, urinary and brain cancers
MEN1	MEN1	Pancreatic tumor, facial angiofibroma, gastrinoma, collagenoma, insulinoma and anterior pituitary tumor
MEN2	RET	Medullary thyroid carcinoma, parathyroid carcinoma, pheochromocytoma
Li-Fraumeni syndrome	TP53	Breast cancer, soft tissue sarcoma, osteosarcoma, brain tumor, acute leukemia, adrenocortical carcinoma, lung adenocarcinoma, colon cancer, pancreatic cancer, prostate cancer, nephroblastoma and phyllodes tumor
Von Hippel-Lindau syndrome	VHL	Pheochromocytoma, hemangioblastoma, high renal cell tumor, pancreatic carcinoma and ampullary paraganglioma adenocarcinoma
Peutz-Jeghers syndrome	STK11	Hamartomatous intestinal polyps, lung cancer, breast cancer, urinary tract cancer, perioral and buccal mucosal pigmentation
Hereditary diffuse gastric cancer	CDH1	Diffuse gastric cancer, lobular breast cancer
Familial RB	RB1	Primary eye cancer
Familial melanoma	CDKN2A (p16)	Melanoma
Fanconi anemia	FANC (A, B, C, D1, D2, E, F, G, I, J, L, M, N), FANCD1/BRCA2, FANCJ/BACH1/BRIP1, FANCN/PALB2	Acute myeloid leukaemia
LS	PMS1, MLH1, MSH2, MSH and PMS2	Cancers of ovary, small intestine, brain and skin
Neurofibromatosis type 1	NF1	Optic nerve glioma, meningioma, hypothalamic tumor, neurofibrosarcoma, rhabdomyosarcoma; Duodenal carcinoid, somatostatinoma, parathyroid adenoma, pheochromocytoma, pilocytic astrocytoma, malignant peripheral nerve sheath tumors, tumors of several other parts of the body, including the central nervous system
Neurofibromatosis type 2	NF2	Meningioma, glioma, vestibular schwannoma
Tuberous sclerosis type 2	TSC2	Myocardial rhabdomyoma, multiple bilateral renal angiomyolipoma, ependymoma, renal carcinoma, giant cell astrocytoma; Benign tumors of the eye, heart, and lungs

表1

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PGT在遗传性肿瘤生殖干预中的应用进展

Progress in the application of PGT in hereditary tumors

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