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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 Silvia 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 Manzella1,21 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 gushiraho 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 bw’abarwayi ba kanseri. kwibasira abaturage bo mu burasirazuba bwa Sisile barabuze. Intego y’ubushakashatsi bwacu kwari ugukora ubushakashatsi ku bijyanye no gukwirakwiza no gukwirakwiza imiti ya virusi itera indwara ya BRCA mu itsinda ry’abarwayi ba BC baturutse mu burasirazuba bwa Sisile no gusuzuma isano ifitanye n’imiterere yihariye ya BC ikoresheje ibisekuruza bizakurikiraho. Kuba hari impinduka zifitanye isano n’ibyiciro by’ibibyimba hamwe n’ikwirakwizwa rya BRCA (17%) ) muri BRCA2. gukumira no kuvura kanseri mubatwara mutation.
Kanseri y'ibere (BC) ni indwara mbi ikunze kugaragara ku isi yose na kanseri ihitana abantu benshi ku bagore.1 Ibiranga 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. G.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. cyane cyane ishinzwe kuragwa BC.Muri ziriya genes, BRCA1 na BRCA2 (aha ni ukuvuga BRCA1 / 2) zerekanye isano ikomeye hamwe no gukura kw'ibibyimba byamabere.9-12 Mubyukuri, imiterere ya mikorobe BRCA1 / 2 yongerera cyane ibyago byubuzima bwa BC kimwe nizindi ndwara mbi, harimo na ovarian, prostate, pancreatic, coloractal, hamwe na melanika ya 80%. CA1 itera indwara (PV) na 69% mubagore 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 bakuze ba BRCA2 kandi bafite impinduka nyinshi. -18 Ikigaragara ni uko ihinduka ry’imihindagurikire muri BRCA1 na BRCA2 ryongera kumva uburyo bwo kuvura 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, n’ubuvuzi bw’amavuriro Kugira ngo hamenyekane neza abantu bakwiriye kwipimisha kuri BRCA1 / 2.22, 23 ni raporo ku itsinda rya BC mu burengerazuba bwa Sisile, amakuru make arahari 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 mu kigo cyitwa “Centre for Experimental Oncology and Hematology” mu bitaro bya Policlinico.Rodolico - San Marco muri Catania. Kuva muri Mutarama 2017 kugeza Werurwe 2021, abarwayi 455 bose bafite amabere na ovarian, melanoma, pancreatic cyangwa kanseri ya prostate boherejwe na laboratoire yo kwisuzumisha kuri BRCA / 2. isesengura.
Ibiranga amateka n’ibinyabuzima (ER, PgR, Imiterere ya HER2, Ki-67, n’icyiciro) cya BC byasuzumwe ku ngero z’ibanze za biopsy cyangwa kubaga, hashingiwe gusa ku bice by’ibibyimba bikabije. Hashingiwe kuri ibyo biranga, BC zashyizwe mu buryo bukurikira: luminal A (ER + na / cyangwa PgR +, HER2-, Ki-67 <20%), Luminal B (ER + na / HER-2, 2+ (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.30,31 Muri ibi bipimo harimo: (i) amateka y’imiryango y’indwara zizwi cyane ziterwa na genoside (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 cyasobanuwe hifashishijwe ibyiciro mpuzamahanga bya Consortium ENIGMA (Ibimenyetso bishingiye kuri Network for Interpreting Germline Mutant Alleles) UP, BRCAEXCHANGE, ClinVar, IARC_LOVD, na UMD.Icyiciro gikubiyemo ibyiciro bitanu bitandukanye by’ingaruka: 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 patogene (icyiciro V).
Kugirango uhabwe ibisobanuro byubuvuzi kuri buri VUS, hakoreshejwe algorithm yo kubara protein zikurikira zo kubara: TASTER TASTER, 33 PROVEAN-SIFT (http://provean.jcvi.org/index.php), POLYPHEN-2 (http: // /genetics.bwh.harvard.edu/pph2/) na Align vgd_input.php) .Ibihinduka byashyizwe mucyiciro cya 1 nicya 2 byafatwaga nkubwoko bwishyamba.
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 hari ibintu byinshi byahinduwe (LGR) .Muri make, ingero za ADN zamaganwe kandi hakoreshwa iperereza ryihariye rya 60 BRCA1 na BRCA2 ryakozwe na progaramu ya ADN hafi ya 60 ya nucleotide. electrophoreis hamwe na Cofalyser.Net software ifatanije nimbonerahamwe ikwiye yihariye 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 mutation byakorewe mu kigo cy’ibitaro bya Policlinico gishinzwe ubuvuzi bwa Oncologiya na Hematologiya. Dukurikije umurongo ngenderwaho wa Sisiliyani (http://www.gurs.regione.sicilia.it/Indicep1.htm, N. 02-Venio) Abarwayi 9 Hariho kanseri y'ibere, kanseri 37 y'intanga, kanseri 16 yandura, kanseri ya prostate 8 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 zanduza indwara zabaye muri BRCA1 na 18 (51.4%) muri BRCA2, naho 5 VUS zabaye muri BRCA1 (17.2%) na 24). isesengura rya MLPA.
Igishushanyo 2. Isesengura ry’imihindagurikire ya BRCA1 na BRCA2 ku barwayi 389 ba kanseri y'ibere..(C) 29.
Amagambo ahinnye: PVs, variant pathogenic variant;VUS, impinduka zidafite akamaro;WT, ubwoko bwa BRCA1 / 2 bukurikirana.
Ubukurikira twakoze ubushakashatsi ku bwiyongere bwa subtekipi 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. 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 ibibyimba B-HER2 +, 3 (16.7%) TNBC na 2 (2) .Nuko rero, ihinduka rya BRCA1 ryiganje mu barwayi ba TNBC, mu gihe ihinduka rya BRCA2 ryiganje mu 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 na gene byaho bya BRCA1 na BRCA2 PV.Muri BRCA1 PV, twabonye variant 7 nucleotide imwe (SNVs), gusiba 6, kwigana 3 no gushiramo 1. Gusa ihinduka rimwe (c.5522delG) ryerekana kuvumburwa gushya.Bisanzwe bya BRCA1 PV byagaragaye muri cC5050_5039d. muri BRCA1 exon 15, bivamo gusimbuza aside amine acide na tyrosine kuri codon 1679, kandi kubera guhindura uburyo bwo guhinduranya hamwe na codon yahanuwe ihagarikwa biganisha ku kugabanuka kwa poroteyine imburagihe. Izindi mpinduka zose zagaragaye murubanza rumwe gusa.Ntabwo, imwe muri PVs yavuzwe yari iherereye mukarere kumvikanyweho (c.4357 + 1).
Kubyerekeranye na PV ya BRCA2, 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. , poroteyine idakora.C.8487 + 1G> Guhinduka bibaho mukarere ka intangiriro ya BRCA2 intron 19 (± 1,2) kandi bigira ingaruka kumyumvire yumvikanyweho, bikavamo guhindagurika bivamo poroteyine idasanzwe cyangwa idahari.C.5851_5854delAGTT ibisubizo byatewe na nucleotide 585 ya nucleotide ya 5 ya nucleotide 58 ibisobanuro byahinduwe hamwe na codon yahanuwe ihagarikwa (p.S1951WfsTer) .Ntabwo, 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 nucleine ya cucine na Gucineine (G). Acide Amino ni aside amine ifite imiterere isa cyane.Iyi mpinduka igira ingaruka kumyanya isanzwe ya mRNA.Ihinduka rya kabiri riherereye mukarere ka intron kandi bikavamo gusimburwa kabiri A na thymine (T) mbere ya exon 13 ya gene irimo BRCA2.Ihinduka rya c.7008-2A> T rishobora kubyara inyandiko-mvugo nyinshi z'uburebure butandukanye.Ikindi kandi, mu itsinda rya BRCA2 PVs.
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 gace ka kanseri y’intanga ngore (OCCR) (mu gace ka 4R). Igishushanyo 4B) .Icyakurikiyeho, twasuzumye aho PV iri muri poroteyine ya BRCA1 na BRCA2. Kuri poroteyine ya BRCA1, twasanze PV eshatu mu cyerekezo hamwe na coil coile, hamwe na mutation ebyiri muri domaine ya BRCT (Igicapo 4A) .Kubera poroteyine ya BRCA2, 4 PVs zashushanyaga kuri OLC ya Oriside na 3. indangarugero (Ishusho 4B).
Igicapo ca 4 Igishushanyo mbonera cya poroteyine za BRCA1 na BRCA2 hamwe n’ahantu hashobora guterwa na virusi. Iyi shusho yerekana ikwirakwizwa rya BRCA1 (A) na BRCA2 (B) itera indwara y’abarwayi ba kanseri y'ibere. Urutonde rwaho (NLS), indangarubuga-coil, indangarubuga ya SQ / TQ (SCD), hamwe na BRCA1 C-terminal (BRCT). ter Akarere (BCCR) hamwe na Ovarian Kanseri ya Cluster Region (OCCR) irerekanwa 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. n'abatwara BRCA2 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 ikoranabuhanga rikurikirana rya ADN ryatumye 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 kuri 20.000 BRCA1 / 2 zashyizwe ahagaragara hakurikijwe Sosiyete y'Abanyamerika y’ubuvuzi bw’ubuvuzi 35 na sisitemu ya ENIGMA.35,36 Birazwi neza ko BRCA1 / 2 ihinduka ry’imiterere ya BRC. ibintu byinshi bihinduka hagati y’igihugu.38,39 Hatuwe n’abaturage bagera kuri miliyoni 5, Sisile 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 bari abagabo.Iki gipimo kiri hejuru yicyari giteganijwe kuri kanseri yamabere yabagabo (1% ya BCs zose) zatewe na BRCA1. bari abakandida kugirango barusheho gusesengura molekuline kugirango birinde ko habaho ihinduka ridahinduka nka PALB2, RAD51C na D, hamwe nabandi.Ibintu bitandukanye bifite akamaro kanini byagarutsweho muri 7% byamasomo BRCA2 VUS yagaragaye.Nubwo iki gisubizo gihuye 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 rusange.2C2. Abayahudi bo muri Ashkenazi bo mu Burayi bwo mu Burasirazuba no Hagati (Polonye, Tchèque), Sloveniya, Otirishiya, Hongiriya, Biyelorusiya n'Ubudage), 44,45 kandi, muri Amerika no muri Arijantine, baherutse gusobanurwa ko ari “imiterere ya germine isubirwamo” ku barwayi b'Abataliyani barwaye BC na OC.Uburyo bwa 34c.514del bwamenyekanye cyane mu barwayi ba kanseri y'ibere.wasanze variant ya c.3253dupA mumiryango imwe n'imwe yo muri Catania.28 PVs ihagarariwe cyane na 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.428dup, c.428 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 yari ikunze 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 PV, c.631 + 1G> A, yabonetse muri BC na OC abarwayi ba Sicile (Agrigento, Siracusa na Ragusa) .28 Ikigaragara ni uko twabonye kubana kwa BRCA2 A na C31. itandukanijwe muburyo bwa cis, nkuko byavuzwe mbere gutya.34,46 Izi mutation ya BRCA2 uble rwose zigaragara 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 na kanseri y'ibere ,.49 Ariko, ibimenyetso byerekeranye nisano iri hagati y’ahantu haterwa na mikorobe hamwe n’indwara ya 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 BRCA2 yari yiganjemo mu turere twa OCCR. CA1 / 2 ihindagurika. 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’icyiciro cy’ibibyimba.Nubwo gusuzuma no gusobanura Ki-67 bikomeje kutavugwaho rumwe, byanze bikunze ko umubare munini w’ubwiyongere bukabije ufitanye isano n’ibyago byo kongera kwandura indwara kandi bikagabanuka kubaho. . -67 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 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, butanga uburenganzira bwo gusuzuma ihinduka ry’imihindagurikire y’imihindagurikire y’imyororokere, y'ubwiyongere bw'amasomo afite ibyago byinshi byo kwandura kanseri bitewe na mutation genetique.
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