ÄϹ¬28NGÏàÐÅÆ·ÅÆÁ¦Á¿

      ͬԴÖØ×éÐÞ¸´£¨homologous recombination repair£¬HRR£©ÊÇDNAË«Á´¶ÏÁÑ£¨double strand break£¬DSB£©µÄÊ×Ñ¡ÐÞ¸´·½Ê½ ¡£Í¬Ô´ÖØ×éÐÞ¸´È±ÏÝ£¨homologous recombination deficiency£¬HRD£©Í¨³£Ö¸Ï¸°ûˮƽÉϵÄHRR ¹¦Ð§ÕÏ°­×´Ì¬£¬¿ÉÓÉHRRÏà¹Ø»ùÒòÅßϵͻ±ä»òÌåϸ°ûÍ»±äÒÔ¼°±í¹ÛÒÅ´«Ê§»îµÈÖî¶àÒòËص¼Ö£¬³£´æÔÚÓÚ¶àÖÖ¶ñÐÔÖ×ÁöÖУ¬ÆäÖÐÔÚÂѳ²°©¡¢ÈéÏÙ°©¡¢ÒÈÏÙµ¼¹Ü°©¡¢Ç°ÁÐÏÙ°©µÈÖ×ÁöÖÐÓÈÆäÍ»³ö¡£HRDÔÚ½üЩÄêÒýÆðÁ˹㷺µÄ¹Ø×¢£¬Öð½¥³ÉΪÓÐÁÙ´²Ç°¾°µÄ·º°©ÖÖÉúÎï±êÖ¾ÎÁÙ´²ÓÃÓÚÌáʾPARPÒÖÖƼÁ¼°²¬ÀàµÈÒ©ÎïµÄÖÎÁÆÁÆЧ¡£

ͼƬÀ´Ô´£ºJ.A. Ledermann et al. , European Journal of Cancer 60 (2016) 49-58

Ò»¡¢×¨¼Ò¹²Ê¶

      HRD ͨ³£Ö¸Ï¸°ûˮƽµÄ HRR ÕÏ°­×´Ì¬£¬HRD »á·¢Éú¿ÉÁ¿»¯µÄ¡¢Îȶ¨µÄ»ùÒò×é¸Ä±ä£¬Ä¿Ç°Ö÷Ҫͨ¹ý LOH¡¢TAI ºÍ LST 3 ¸öÖ¸±êµÄ×ۺϼì²âµÃ³ö »ùÒò×é²»Îȶ¨ÆÀ·Ö£¨genomic instability score£¬GIS£©£¬ÁÙ´²Êµ¼ùÖÐÒÔBRCA1/2»ùÒòÖ²¡ÐÔÍ»±äÓëGISÆÀ¹ÀÖ×ÁöHRD״̬¡£¼øÓÚHRRͨ·ÒÔ¼°Ï¸°ûÐźÅͨ·µÄÅÓ´óÐÔ£¬Í¨¹ýÁÙ´²¼ì²âÒªÁìʵÏÖÖ×Áöϸ°û HRD È«Ãæ¶ø׼ȷµÄÆÀ¹ÀÈÔ¾ßÌôÕ½ ¡£

Öйú°©Ö¢·ÀÖÎÔÓÖ¾ 2021Äê8ÔµÚ13¾íµÚ4ÆÚ

      ×Ô2012ÄêÒÔÀ´£¬ÔÓºÏÐÔȱʧ£¨loss of heterozygosity£¬LOH£©¡¢¶ËÁ£µÈλ»ùÒò²»Æ½ºâ£¨telomeric allelic imbalance£¬ TAI£©¡¢´óƬ¶ÎǨÒÆ£¨large?scale state transition£¬LST£©µÈ±»×÷Ϊ»ùÒò×éñ£ºÛ±êÖ¾ÎÒÔÁ¿»¯»ùÒò×éñ£ºÛµÄˮƽ¡£

ͼƬÀ´Ô´£ºÍøÂç

¶þ¡¢ÁÙ´²¼ÛÖµ£ºÖ¸µ¼PARPÒÖÖƼÁÓÃÒ©

      HRD »á·¢ÉúÌض¨µÄ¡¢¿ÉÁ¿»¯µÄ¡¢Îȶ¨µÄ»ùÒò×é¸Ä±ä£¬¿Éͨ¹ý½¨Á¢»ùÓÚ»ùÒò×éÌØÕ÷·ÖÎöµÄÆÀ¹ÀÌåϵÀ´Ô¤²âÖ×ÁöHRD״̬¼°Æäˮƽ£¬ÒѳÉΪÍíÆÚÂѳ²°©»¼ÕßÁÙ´²Ó¦ÓþÛÏÙÜÕ¶þÁ×ËáºËÌǾۺÏø£Ûpoly£¨ADP?ribose£©polymerase£¬PARP£ÝÒÖÖƼÁµÄÐÂÐÍÉúÎï±êÖ¾Îï¡£

ͼƬÀ´Ô´£ºÍøÂç

      Ä¿Ç°È«ÇòÒÑÓжàÖÖ PARP ÒÖÖƼÁ»ñÅúÉÏÊУ¬ÈçÓÉFDAÅú×¼µÄ°ÂÀ­ÅÁÀû£¨Olaparib£©£¬Â³¿¨ÅÁÀû£¨Rucaparib£©£¬ ÄáÀ­ÅÁÀû£¨Niraparib£©£¬ËûÀ­ßòÅÁÀû£¨Talazoparib£©ÒÔ¼°½üÆÚÓÉ NMPA Åú×¼µÄ·úßòÅÁÀû£¨Fluzoparib£©ºÍÅÁÃ×ÅÁÀû£¨Pamiparib£©µÈ£¬ÒÑÏà¼ÌÔÚÂѳ²°©¡¢Ç°ÁÐÏÙ°©¡¢ÈéÏÙ°©¡¢ÒÈÏÙ°©µÈÖ×ÁöÖлñÅúÖî¶àÊÊÓ¦Ö¤£¬Óë´Ëͬʱ£¬HRDÁÙ´²¼ì²â×÷Ϊ PARP ÒÖÖƼÁÖØÒªµÄÁÆЧԤ²â±êÖ¾ÎïÒ²µÃÒÔѸËÙÉú³¤¡£

Èý¡¢ÄϹ¬28NGÏàÐÅÆ·ÅÆÁ¦Á¿Í¬Ô´ÖØ×éȱÏÝHRDÆÀ¹À

      ÎÒÃÇÈ«ÐÂÍƳöͬԴÖØ×éȱÏÝHRDÆÀ¹À£¬½ô¿ÛHRD ×÷Ϊ½ÏÎȶ¨µÄ¶ñÐÔÖ×Áö·Ö×Ó±êÖ¾£¬¾«È·Ô¤²âPARPÒÖÖƼÁÔÚÏà¹Ø°©ÖÖµÄÁÆЧ¡£

²úÎïÓÅÊÆ

1¡¢Áé»î×éºÏ——HRD+HRR+BRCA1/2

2¡¢¸öÐÔ¶¨ÖÆ——¾«×¼¶¨Î»¼Ò×åÐÔÒÅ´«·çÏÕ

3¡¢ÁìÏȿƼ¼——¸üÈ«ÃæPARPÒÖÖƼÁÁÆЧÆÀ¹À

¼¼ÊõÌصã

¹ãØ­²îÒìÆ·¼¶£¨I¼¶¡¢II¼¶¡¢III¼¶£©»ùÒòÁýÕÖ¹ã

È«Ø­Í»±äÀàÐÍ£¨SNP¡¢CNV¡¢FusionµÈ£©½âÎöÈ«

¸ßØ­¸ß¾«¶È¼ì²â£¬¿É¼ì0.1%µÍƵ±äÒì

¿ìحȨÍþÊý¾Ý¿â¸üпì

ÊÊÓÃÈËȺ

¢Ù Âѳ²°©¡¢ÈéÏÙ°©»¼Õß

¢Ú Ç°ÁÐÏÙ°©¡¢ÒÈÏÙ°©µÈÆäËûʵÌåÁö»¼Õß

Ñù±¾ÀàÐÍ

×éÖ¯/ѪҺ

²Î¿¼ÎÄÏ×

[1] Truong LN, Li Y, Shi LZ, Hwang PY-H, He J, Wang H, et al. Microhomology-mediated end joining and homologous recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells. Proc Natl Acad Sci USA 2013;110(19):7720-5.

[2] Arnaudeau C, Lundin C, Helleday T. DNA double-strand breaks associated with replication forks are predominantly repaired by homologous recombination involving an exchange mechanism in mammalian cells1. J Mol Biol 2001;307(5):1235-45.

[3] LIPS E H£¬LADDACH N£¬SAVOLA S P£¬et al. Quantitative copy number analysis by Multiplex Ligation?dependent Probe Amplification£¨MLPA£©of BRCA1?associated breast cancer regions identifies BRCAness£ÛJ£Ý.Breast Cancer Res£¬2011£¬13£¨5£©£ºR107.