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作者 Stella S, Vitale SR, Martorana F, Massimino M, Pavone G, Lanzafame K, Bianca S, Barone C, Gorgone C, Fichera M, Manzella L
Stefania Stella, 1,2 Siliviya Rita Vitale, 1,2 Federica Martorana, 1,2 Michele Massimino, 1,2 Giuliana Pavone, 3 Katia Lanzafame, 3 Sebastiano Bianca, 4 Chiara Barone, 5 Cristina Gorgone, 6 Marco Fichera, 6, 7 Livia Manzella1 Ubutaliyani; Ikigo 2 cy’ubushakashatsi bwa Oncology na Hematology, AOU Policlinico “G.Rodolico - San Marco”, Catania, 95123, Ubutaliyani; 3 Oncology yubuvuzi, AOU Policlinico “G. Rodolico - San Marco”, Catania, 95123, Ubutaliyani; 4 Ubuvuzi bwubuvuzi, ARNAS Garibaldi, Catania, 95123, Ubutaliyani; 5 Ubuvuzi bwubuvuzi, ASP, Syracuse, 96100, Ubutaliyani; Ishami ry’ubumenyi bw’ibinyabuzima n’ibinyabuzima, kaminuza ya Catania, Ubuvuzi bw’ubuvuzi, Catania, Ubutaliyani, 95123; 7Oasi Ikigo Cyubushakashatsi-IRCCS, Troina, 94018, Ubutaliyani Itumanaho: Stefania Stella, tel +39 095 378 1946, imeri [imeri irinzwe]; [imeri irinzwe] Intego: Guhindura imiterere ya Germline muri BRCA1 na BRCA2 no gushyiraho kanseri yamabere (BC), ovary (OC) nibindi bifitanye isano na kanseri y'ubuzima bwe bwose. Gupima gene ya BRCA ni urufunguzo rwo gusuzuma ibyago by’umuntu ku giti cye, ndetse no gushakisha uburyo bwo gukumira abatwara ubuzima bwiza hamwe n’ubudozi buvura abarwayi ba kanseri. Imiryango ya Sisiliyani, ubushakashatsi bwibanze ku baturage bo mu burasirazuba bwa Sisile burabuze. Intego y’ubushakashatsi bwacu kwari ugukora ubushakashatsi ku ikwirakwizwa ry’ikwirakwizwa ry’imisemburo ya BRCA yanduye mu itsinda ry’abarwayi ba BC baturutse mu burasirazuba bwa Sisile no gusuzuma isano ifitanye n’imiterere yihariye ya BC bakoresheje ibisekuruza bizakurikiraho. . umurage BC.Buri rusange, aya makuru ajyanye nibimenyetso byabanjirije gushyigikira isuzuma rya BRCA mu rwego rwo gukumira no kuvura kanseri mu batwara mutation.
Kanseri y'ibere (BC) ni indwara mbi ikunze kugaragara ku isi yose na kanseri ihitana abantu benshi mu bagore.1 Ibinyabuzima bigena imiterere ya BC n'imyitwarire ya kliniki byakozweho ubushakashatsi bwimbitse kandi bisobanurwa mu gihe runaka. Mubyukuri, ibimenyetso byinshi bya surrogate kuri ubu bikoreshwa mu gushyira BC mu bwoko butandukanye bwa molekile. Urwego rwa Ki-67 hamwe n’ibibyimba (G) .2 Guhuza izi mpinduka byagaragaje ibyiciro bya BC bikurikira: 1) Ibibyimba bya Luminal, byerekana imvugo ya ER na / cyangwa PgR, bingana na 75% bya BC.Ibibyimba byongeye kugabanywa muri Luminal A, mugihe Ki-67 yari munsi ya 20% na HER2 itari nziza, na Luminal B, mugihe Ki-67 yari ihwanye na hejuru ya 20%; 2) Ibibyimba bya HER2 + ER na PgR bibi ariko byerekana amplification ya HER2. Iri tsinda rifite 10% yibibyimba byose byamabere; 3) Kanseri y'ibere inshuro eshatu (TNBC), itagaragaza imvugo ya ER na PgR hamwe na HER2 amplification, ihwanye na 15% bya kanseri y'ibere.2-4
Muri ubu bwoko bwa BC, urwego rwibibyimba no gukwirakwiza byerekana biomarkers ihuza ibice kandi byigenga bifitanye isano no kwibasira ibibyimba no guhanura.5,6
Usibye ibinyabuzima bimaze kuvugwa, uruhare rw’imihindagurikire y’irondakoko iganisha ku iterambere rya BC rwabaye ingirakamaro mu myaka mike ishize.7 Ibibyimba bigera kuri 1 kuri 10 byaragizwe umurage bitewe n’imihindagurikire ya germine mu bwoko bwihariye.8. RAD51D) ishinzwe cyane cyane umurage wa BC.Muri ziriya genes, BRCA1 na BRCA2 (aha ni ukuvuga BRCA1 / 2) yerekanye isano ikomeye cyane hamwe no gukura kw'ibibyimba byamabere.9-12 Mubyukuri, ihinduka ryimiterere ya germine BRCA1 / 2 ryongera cyane ibyago byubuzima bwa BC kimwe nizindi ndwara mbi, harimo na ovary, prostate, pancreatic, imyaka, indwara ya BC ni 72% ku bagore bafite BRCA1 itera indwara (PV) na 69% ku bagore bafite BRCA2 PV.14
Ikigaragara ni uko igitabo giherutse kwerekana ko ibyago bya BC biterwa n'ubwoko bwa PV.Mu byukuri, ugereranije no guhinduranya indwara ziterwa na virusi, ibintu bitangaje bya misense, cyane cyane muri gene ya BRCA1, bifitanye isano no kugabanuka kwa BC, cyane cyane ku bagore bakuze.15
Kubaho kwa BRCA1 cyangwa BRCA2 PV byari bifitanye isano nuburyo butandukanye bwibinyabuzima n’amavuriro.16,17 BC ifitanye isano na BRCA1 ikunda kwibasirwa n’amavuriro, itandukanijwe nabi, kandi ikwirakwira cyane.Ibibyimba bikunze kuba bibi inshuro eshatu kandi bifite imyaka yo gutangira.Ibibyimba biboneka mu barwayi ba BRCA2 bahinduwe mubisanzwe byerekana ibyiciro byinshi kandi bitandukana cyane. ku bantu bakuze.16-18 Ikigaragara ni uko ihinduka ry’imiterere muri BRCA1 na BRCA2 ryongera ubukangurambaga ku buvuzi bwihariye, harimo umunyu wa platine ndetse n’ibiyobyabwenge bigamije nka poly (ADP-ribose) polymerase inhibitor (PARPi) .19,20
Mu myaka mike ishize, ishyirwa mu bikorwa ry’ibisekuruza bizakurikiraho (NGS) mu bikorwa by’ubuvuzi byatumye umubare w’abarwayi ba BC wiyongera kwipimisha molekuline kuri syndromes zandura kanseri, harimo na BRCA1 / 2.21 Icyarimwe, ibisobanuro bishingiye ku ngingo zifatika zerekeye amateka y’umuryango, imiterere y’imiterere y’imiterere, n’ubuvuzi bw’amavuriro kugira ngo hamenyekane neza abantu bakwiriye kwipimisha kuri BRCA1 / 2.2, 23 uturere.24-27 Nubwo hari amakuru kuri cohort ya BC mu burengerazuba bwa Sisile, amakuru make araboneka kuri BRCA1 / 2 kwerekanwa muburasirazuba bwa Sisile.28,29
Turasobanura hano ibisubizo bya germine BRCA1 / 2 kwipimisha ku barwayi ba BC baturutse mu burasirazuba bwa Sisile, bikarushaho guhuza ihinduka ry’imiterere ya BRCA1 cyangwa BRCA2 hamwe n’ibintu nyamukuru by’amavuriro biranga ibyo bibyimba.
Ubushakashatsi bwisubireho bwakorewe muri "Centre for Experimental Oncology and Hematology" mu Bitaro bya Policlinico.Rodolico - San Marco muri Catania. Kuva muri Mutarama 2017 kugeza Werurwe 2021, abarwayi 455 bafite amabere na ovarian, melanoma, kanseri yandura cyangwa prostate boherejwe muri laboratoire yacu yo kwisuzumisha kuri BRCA / 2. kumenyeshwa amakuru mbere yisesengura rya molekile.
Ibiranga amateka n’ibinyabuzima (ER, PgR, HER2 status, Ki-67, nicyiciro) cya BC byasuzumwe kuri biopsy yibanze cyangwa kubagwa, harebwa gusa ibibyimba byibibyimba bikabije. Hashingiwe kuri ibyo biranga, BC yashyizwe mubyiciro bikurikira: luminal A (ER + na / cyangwa PgR +, HER2-, Ki-67 <20%), Luminal B (ER + na / P / R2 +) luminal B-HER2 + (ER na / cyangwa PgR +, HER2 +), HER2 + (ER na PgR-, HER2 +) cyangwa bitatu bibi (ER na PgR-, HER2-).
Mbere yo gusuzuma imiterere ya mutation ya BRCA1 na BRCA2, itsinda ry’abantu benshi barimo oncologue, genetiste, na psychologue bakoze inama kuri genetics yibibyimba kuri buri murwayi kugirango bamenye niba BRCA1 na / cyangwa BRCA1. cyangwa abantu bafite ibyago byinshi byo kwandura PV muri gene ya BRCA2. Guhitamo abarwayi byakozwe hakurikijwe amabwiriza y’umuryango w’abataliyani w’ubuvuzi Oncology (AIOM) hamwe n’ibyifuzo bya Sisiliyani yaho.30,31 Muri ibi bipimo harimo: (i) amateka y’imiryango y’indwara zizwi ziterwa na virusi (urugero, BRCA1, BRCA2, TP53, PTEN); (ii) abagabo bafite BC; (iii) abafite BC na OC; (iv) abagore bafite BC
Amazina yose atandukanye yakurikije umurongo ngenderwaho wubu wa Human Genome Variation Consortium, iboneka kumurongo (HGVS, http://www.hgvs.org/mutnomen).Ikamaro kivuriro rya variant ya BRCA1 / 2 ryasobanuwe hifashishijwe ibyiciro bya International Consortium ENIGMA (Network-Network Network for Interpreting Germline Mutant Alleles) Ububikoshingiro nka ARUP, BRCAEXCHANGE, ClinVar, IARC_LOVD, na UMD.Icyiciro kirimo ibyiciro bitanu bitandukanye by’ibyago: benign (icyiciro cya I), birashoboka ko ari byiza (icyiciro cya II), impinduka zidafite akamaro kanini (VUS, icyiciro cya III), birashoboka ko bitera indwara (icyiciro cya IV), hamwe na porogenike (imikorere ya V).
Kugenera ibisobanuro byubuvuzi kuri buri VUS, hakoreshejwe algorithm yo kubara protein ikurikira yo kubara: TASTER TASTER, 33 PROVEAN-SIFT (http://provean.jcvi.org/index.php), POLYPHEN-2 (http: // /genetics.bwh.harvard.edu/pph2/) na Align. (http://agvgd.hci.utah.edu/agvgd_input.php)
Urutonde rwa Sanger rwemeje ko buri variant ishobora gutera indwara. Muri make, primers yihariye yateguwe kuri buri variant yamenyekanye hakoreshejwe urutonde rwa gene ya BRCA1 na BRCA2 (NG_005905.2, NM_007294.3 na NG_012772.3, NM_000059.3) .Nuko rero, intego ya PCR yakurikiwe na Sanger.
Abarwayi bapimye nabi gene ya BRCA1 / 2 bapimwe na multiplex ligation-iterwa na probe amplification (MLPA) bakurikije amabwiriza yabakozwe kugirango basuzume ko habaho ihindagurika rinini rya genoside (LGR) .Mu magambo make, ingero za ADN zamaganwe kandi hakoreshwa iperereza ryihariye rya BRCA1 na BRCA2 rigizwe n’ibicuruzwa byihariye bya PCR, bigizwe na nucleotide zingana na 60. gusesengurwa na capillary electrophoresis hamwe na Cofalyser.Net software ifatanije nimbonerahamwe ikwiye ya Cofalyser (www.mrcholland.com).
Guhitamo ivuriro ryatoranijwe (urwego rwamateka na Ki-67% yo gukwirakwiza) byajyanye no kuba hari BRCA1 / 2 PV, ubarwa ukoresheje porogaramu ya Prism iburana 8.4 ukoresheje ikizamini nyacyo cya Fisher ukeka ko p-agaciro <0.05 ari ngombwa.
Hagati ya Mutarama 2017 na Werurwe 2021, hasuzumwe abarwayi 455 kugira ngo bahindurwe na germine BRCA1 / 2. Guhindura mutima byakorewe mu kigo cy’ibitaro bya Policlinico gishinzwe ubushakashatsi kuri Oncology na Hematology. Dukurikije umurongo ngenderwaho wa Sisiliyani (http://www.gurs.regione.sicilia.it/Indicep1.htm, N. 02-Venio). Marco ”muri rusange, abarwayi 389 Habayeho kanseri y'ibere, kanseri y'intanga 37, kanseri 16 yandura, kanseri 8 ya prostate na melanoma 5. Ikwirakwizwa ry'abarwayi ukurikije ubwoko bwa kanseri n'ibisubizo by'isesengura bigaragara ku gishushanyo 1.
Igicapo 1 kirerekana imbonerahamwe yerekana ishusho rusange yubushakashatsi. Abarwayi bafite ibere, melanoma, pancreatic, prostate, cyangwa ova yintanga zapimwe kugirango bahindure ihinduka ryimiterere ya gen BRCA1 na BRCA2.
Amagambo ahinnye: PVs, variant pathogenic variant; VUS, impinduka zidafite akamaro; WT, ubwoko bwa BRCA1 / 2 bukurikirana.
Twahisemo kwibanda ku bushakashatsi bwacu kuri kanseri y'ibere.Abarwayi bari bafite hagati yimyaka 49 (intera 23-89) kandi bari biganjemo abagore (n = 376, cyangwa 97%).
Muri ayo masomo, 64 (17%) yari afite ihinduka rya BRCA1 / 2 kandi bose bari igitsina gore. Mirongo itatu na batanu (9%) bafite PV na 29 (7.5%) bafite VUS.Icyiciro cumi na birindwi (48,6%) muri 35 za virusi zitera indwara zabaye muri BRCA1 na 18 (51.4%) muri BRCA2, naho 5 VUS zabaye muri BRCA1 (17.2%) na 24 2) .LGR ntabwo yari ihari mu isesengura rya MLPA.
Igishushanyo cya 2. Isesengura ry’imihindagurikire ya BRCA1 na BRCA2 ku barwayi ba kanseri y'ibere 389. . (C) 29.
Amagambo ahinnye: PVs, variant pathogenic variant; VUS, impinduka zidafite akamaro; WT, ubwoko bwa BRCA1 / 2 bukurikirana.
Ubukurikira twakoze iperereza ku bwiyongere bwa subtypes ya BC ya BC ku barwayi bafite BRCA1 / 2 PV.Ikwirakwizwa ryarimo 2 (5.7%) luminal A, 15 (42.9%) luminal B, 3 (8,6%) luminal B-HER2 +, 2 (5.7%) HER2 + na 13 (37.1%) abarwayi ba TNBC. Indwara ya HER2 +, na 10 (58.8%) bari bafite TNBC. Ibibyimba bidafite ihinduka rya BRCA1 byari luminal A cyangwa luminal B-HER2 + (Ishusho 3) .Mu itsinda rya BRCA2 ryiza, ibibyimba 10 (55,6%) byari luminal B, 3 (16.7%) byari Luminal B-HER2 +, 3 (16.7%). Ibibyimba bya HER2 + byari bihari muri iri tsinda. Kubwibyo, ihinduka rya BRCA1 ryiganje ku barwayi ba TNBC, mu gihe ihinduka rya BRCA2 ryiganje cyane ku bantu B lumen B.
Igicapo ca 3 Ikwirakwizwa rya kanseri y'ibere ku barwayi bafite indwara ziterwa na virusi muri BRCA1 na BRCA2.
Amagambo ahinnye: PVs, variant pathogenic variant; HER2 +, ibyorezo byindwara ya epidermal reseptor 2 nziza; TNBC, kanseri y'ibere inshuro eshatu.
Icyakurikiyeho, twasuzumye ubwoko bwa gene na BRCA1 na BRCA2 PV.Muri BRCA1 PV, twabonye variant 7 nucleotide imwe (SNVs), gusiba 6, kwigana 3 no gushiramo 1. Gusa ihinduka rya mutation imwe (c.5522delG) ryerekana ivumburwa rishya. .
Kubijyanye na BRCA2 PV, twabonye gusiba 6, SNVs 6 na duplications 2.Nta mpinduka zabonetse ni shyashya.Imihindagurikire itatu yagarutse mu baturage bacu, c.428dup na c.8487 + 1G> Yagaragaye mu ngingo 3, ikurikirwa na c.5851_5854delAGTT yagaruwe mu manza ebyiri.Cte ya C2 poroteyine yagabanijwe, idakora.C.8487 + 1G> Guhinduka bibera mu karere gakomeye ka BRCA2 intron 19 (± 1,2) kandi bigira ingaruka ku bwumvikane buke, bikavamo ihinduka rya poroteyine idasanzwe cyangwa idahari.C.5851_5854delAGTT ihindagurika rya 585 kuri nucleotide iterwa na 585 nucleotide 10 ya gene ya BRCA2 kandi bivamo guhinduranya ibisobanuro hamwe na codon yahanuwe ihagarikwa (p.S1951WfsTer) .Ntabwo byavuzwe, nkuko byavuzwe mbere, impinduka zombi c.631G> A na c.7008-2A> T zagaragaye kumurwayi umwe.34 Guhinduka kwa mbere birimo gusimbuza adenosine (A) muri Gineine ya Gine. isoleucine kuri codon 211, aside isoleucine Amino ni aside amine ifite imitungo isa cyane.Iyi mpinduka igira ingaruka kumyanya isanzwe ya mRNA.Ihinduka rya kabiri riherereye mukarere ka intron kandi bivamo gusimburwa kabiri A na thymine (T) mbere ya exon 13 ya gene irimo kodegisi ya BRCA2.Ihinduka rya c.7008-2A> T. (22.2%) bari intangiriro.
Twahise dushushanya ihinduka ry’imiterere ihindagurika rya BRCA1 / 2 mu bice bikora ndetse no mu turere duhuza poroteyine (Ishusho ya 4) .Mu gene ya BRCA1, 50% ya PV yari iherereye mu gace ka kanseri y'ibere (BCCR), mu gihe 22% bya mutation byari biherereye mu karere ka kanseri y’intanga ngore (OCCR) (mu gace ka 4C). . oligo / oligosaccharide-ihuza (OB) n'umunara (T) domaine (Ishusho 4B).
Igicapo ca 4 Igishushanyo mbonera cya poroteyine za BRCA1 na BRCA2 hamwe n’ahantu hashobora guterwa na virusi. Iyi shusho yerekana ikwirakwizwa ry’indwara ya BRCA1 (A) na BRCA2 (B) y’indwara ziterwa na kanseri y'ibere. . ruhande.Ibice byitwa Akarere ka Kanseri y'ibere (BCCR) hamwe n'akarere ka Ovarian Kanseri (OCCR) byerekanwe hepfo. * Yerekana ihinduka ryerekana ihinduka rya code.
Twahise dukora iperereza kuri clinique yubuvuzi ya BC ishobora guhuza no kuba hari BRCA1 / 2 PV. Inyandiko zuzuye zamavuriro zarabonetse kubarwayi 181 BRCA1 / 2-babi (abatari abatwara) nabatwara bose (n = 35) .Hariho isano riri hagati yikwirakwizwa ryikibyimba nicyiciro.
Twabaze ikwirakwizwa rya Ki-67 dushingiye kuri median cohort yacu (25%, intera <10-90%) .Ibintu bifite Ki-67 <25% byasobanuwe nk "Ki-67 low yo hasi, mugihe abantu bafite agaciro ≥ 25% bafatwaga nk" Ki-67 ″ .Itandukaniro rikomeye rya Ki-67 (p <0.01) ryabonetse hagati yabatwara na BRCA1 PV.
Igicapo 5 Isano rya Ki-67 hamwe nogukwirakwiza amanota kubagore ba kanseri yamabere hamwe na BRCA1 na BRCA2 PVs. amasomo, BRCA1 na BRCA2 abatwara PVs).
Mu buryo nk'ubwo, twasuzumye niba igipimo cy’ibibyimba gifitanye isano no kuba hari BRCA1 / 2 PV.Kuko G1 BC idahari mu baturage bacu, twagabanyije abarwayi mu matsinda abiri (G2 cyangwa G3) .Ntibihuye n’ibisubizo bya Ki-67, isesengura ryagaragaje isano iri hagati y’imibare y’ibibyimba na mutation ya BRCA1 (ugereranije na 0.005).
Iterambere mu ikorana buhanga rya ADN ryatumye habaho iterambere ritigeze ribaho mu isuzuma ry’irondakarere rya BRCA1 / 2, rikagira ingaruka zikomeye ku barwayi bafite amateka y’umuryango wa kanseri. Kugeza ubu, hamenyekanye impinduka zigera ku 20.000 BRCA1 / 2 zashyizwe ku rutonde hakurikijwe Sosiyete y'Abanyamerika y’ubuvuzi bw’ubuvuzi 35 hamwe na sisitemu ya ENIGMA.35,36 Birazwi neza ko BRCA1 / 2 ihinduka ry’imiterere ya BRC. kugeza kuri 37%, byerekana itandukaniro rinini hagati y’igihugu.38,39 Hatuwe n’abaturage bagera kuri miliyoni 5, Sicile n’akarere ka gatanu mu bunini mu Butaliyani ukurikije umubare w’abaturage. Nubwo amakuru ariho ku ikwirakwizwa rya BRCA1 / 2 mu burengerazuba bwa Sisile, nta bimenyetso bifatika biri mu burasirazuba bw'ikirwa.
Ubushakashatsi bwacu ni imwe muri raporo za mbere zerekeye indwara ya BRCA1 / 2 PV ku barwayi ba BC mu burasirazuba bwa Sisile.28 Twibanze ku isesengura ryacu kuri BC, kubera ko iyi ari yo ndwara ikunze kugaragara mu itsinda ryacu.
Mugihe cyo gupima abarwayi 389 BC, 9% batwaye PVs ya BRCA1 / 2, bagabanijwe neza hagati ya BRCA1 na BRCA2.Ibisubizo birahuye nibyavuzwe mbere mubatuye mubutaliyani.28 Igishimishije, 3% (13/389) byitsinda ryacu ryari abagabo.Iki gipimo kiri hejuru yicyari giteganijwe kuri kanseri yamabere yabagabo (1% ya BCs zose). BRCA1 / 2 PV, nuko rero bari abakandida kugirango barusheho gusesengura molekuline kugirango birinde ko habaho ihinduka ridahinduka nka PALB2, RAD51C na D, nibindi.Ibintu bitandukanye bifite akamaro kanini byagarutsweho muri 7% byamasomo BRCA2 VUS yagaragaye.Nubwo ibisubizo bihuye nibimenyetso byabanjirije.28,41,42.
Igihe twasesenguye ikwirakwizwa rya molekuline ya BC mu bagore ba mutant ba BRCA1 / 2, twemeje amashyirahamwe azwi hagati ya TNBC na BRCA1 PV (58.8%) no hagati ya Luminal B BC na BRCA2 PV (55,6%).
Turahita twibanda kubwoko na BRCA1 / 2 PV.Muri cohort yacu, PV ya BRCA1 yakunze kugaragara yari c.5035_5039delCTAAT.Nubwo Incorvaia nibindi. ntabwo yasobanuye iyi variant muri cohort yabo ya Sisiliyani, abandi banditsi bavuze ko ari mikorobe BRCA1 PV.34 PV nyinshi za BRCA1 zabonetse muri cohort yacu - urugero c.181T> G, c.514del, c.3253dupA na c.5266dupC - byagaragaye muri Sicily.28 Muri aba bombi, BRCA1. c. Messina. Birashimishije, ndetse na Incorvaia n'abandi. wasanze variant ya c.3253dupA mumiryango imwe n'imwe yo muri Catania.28 PVs zihagarariye BRCA2 ni c.428dup, c.5851_5854delAGTT hamwe na variant idasanzwe c.8487 + 1G> A, byavuzwe muburyo burambuye 28 mumurwayi wo muri Palermo hamwe na c.428d_G Sicile, cyane cyane mu turere twa Trapani na Palermo, mu gihe c.5851_5854delAGTT PV yagaragaye mu ngo zo mu majyaruguru y'uburengerazuba bwa Sisile. 8487 + 1G> Impinduka yakunze kugaragara cyane mu masomo yo muri Messina, Palermo, na Caltanissetta.28 Rebbeck n'abandi. mbere yasobanuye ihinduka rya c.5851_5854delAGTT muri Kolombiya.37 Ubundi PV ya BRCA2, c.631 + 1G> A, yabonetse muri BC na OC abarwayi bo muri Sicile (Agrigento, Siracusa na Ragusa) .28 Ikigaragara ni uko twabonye kubana kwa BRCA2 imwe na c.6. ibyo twakekaga ko bitandukanijwe muburyo bwa cis, nkuko byavuzwe mbere.34,46 Izi mutation za BRCA2 uble zikunze kugaragara cyane mukarere k'Ubutaliyani kandi wasangaga zishyiraho code zo guhagarika imburagihe, bikagira ingaruka ku ntumwa RNA itera kandi bigatuma poroteyine ya BRCA2 inanirwa.47,48
Twashushanyije kandi PVCA ya BRCA1 na BRCA2 mu turere twa OCCR na BCCR dushyiramo poroteyine na gen. Utu turere twasobanuwe na Rebbeck n'abandi. nk'ahantu hashobora kwibasirwa na kanseri yintanga n’amabere, uko bikurikirana.49 Icyakora, ibimenyetso byerekeranye n’isano riri hagati y’ahantu haterwa na germine hamwe na kanseri y’amabere cyangwa intanga ngore bikomeje kutavugwaho rumwe.28,50-52 Mu baturage bacu, PVs za BRCA1 zari ziganje cyane mu karere ka BCCR, mu gihe PVCA za BRCA2 zari ziherereye mu karere ka OCCR. umubare w'abarwayi bafite ihinduka rya BRCA1 / 2. Uhereye kuri poroteyine ya poroteyine, PVs za BRCA1 zitangwa kuri poroteyine zose, kandi ibyahinduwe na BRCA2 biboneka cyane muri BRC isubiramo.
Hanyuma, twahujije ibiranga ivuriro rya BC hamwe na BRCA1 / 2 PV.Kubera umubare muto w'abarwayi barimo, twasanze gusa isano iri hagati ya Ki-67 n'ikibyimba.Nubwo gusuzuma no gusobanura Ki-67 bikomeje kutavugwaho rumwe, byanze bikunze ko umubare munini w'ubwiyongere bukabije ufitanye isano no kongera ibyago byo kwandura indwara kandi bikagabanuka kubaho. ku baturage bacu barwayi ba mutation ya BRCA1 / 2, ifite hagati ya Ki-67 yo hagati ya 25% .Iki cyerekezo kiri hejuru ya Ki-67 gishobora gusobanurwa nubwinshi bwibibyimba byacu bya Luminal B na TNBC, muri byo harimo ibibyimba bike bya luminal A byari bihari.Nyamara, ibimenyetso bimwe bisa nkaho byerekana ko ihuriro ryinshi rya Ki-67 (25-30) ntibitangaje. Ibibaho hagati ya Ki-67 yo hejuru hamwe n amanota no kuba hari BRCA1 PV.Mu byukuri, ibibyimba bifitanye isano na BRCA1 biranga TNBC kandi byerekana ibintu bikaze.16,17
Mu gusoza, ubu bushakashatsi butanga raporo yerekana uko ihinduka ry’imiterere ya BRCA1 / 2 mu itsinda rya BC ryaturutse mu burasirazuba bwa Sisile.Muri rusange, ibyo twabonye bihuye n’ibimenyetso byabanjirije iki, haba mu bijyanye n’ubwiyongere bw’imihindagurikire y’imiterere n’imiterere y’amavuriro muri BC.Ubushakashatsi bwinshi bwakozwe ku baturage benshi b’abarwayi ba BRCA1 / 2-bahinduye BC, butangwa na PVT butandukanye. kumenya no gucunga neza umubare w’amasomo yiyongera ku byago bya kanseri bitewe n’imihindagurikire y’imiterere.
Twemeje ko abarwayi basinyiye uruhushya rwo kumenyekanisha kurekura ibibyimba byabo mu buryo butazwi hagamijwe ubushakashatsi. Abarwayi bose basinye uruhushya rwanditse babimenyeshejwe hakurikijwe Itangazo rya Helsinki. Dukurikije politiki ya AOU Policlinico “G.Rodolico - S.Marco”, ubu bushakashatsi bwasonewe isuzuma ry’imyitwarire kubera ko isesengura rya BRCA1 / 2 ryakozwe hakurikijwe ubushakashatsi bw’ubuvuzi kandi abarwayi bose batanze uruhushya rwanditse.
Turashimira Prof. Paolo Vigneri ku bw'ubufasha yagize mu kwita ku barwayi ba kanseri y'ibere nk'uko byasabwe na komite ishinzwe imyitwarire.
Federica Martorana avuga icyubahiro kuva Istituto Gentili, Eli Lilly, Novartis, Pfizer. Abandi banditsi batangaza ko nta makimbirane ashimishije muri iki gikorwa.
1. Sung H, Ferlay J, Siegel RL, nibindi
Igihe cyo kohereza: Apr-15-2022
