imyanitov

44 %
56 %
Information about imyanitov
Education

Published on February 28, 2008

Author: Maurizio

Source: authorstream.com

Slide1:  MOLECULAR PATHOGENESIS OF BILATERAL BREAST CANCER Evgeny Imyanitov N.N. Petrov Institute of Oncology, St.-Petersburg Project 03-4234 Co-ordinator: Cees Cornelisse Leiden University BILATERAL BREAST CANCER:  BILATERAL BREAST CANCER OFTEN MISTAKENLY IDENTIFIED TOGETHER WITH FAMILIAL BC CLINICAL DEFINITIONS VARY POORLY DESCRIBED EVEN ON THE CLINICAL LEVEL NO DATA ON MOLECULAR PATHOGENESIS CLINICAL DIAGNOSIS - biBC OR METASTASIS?:  CLINICAL DIAGNOSIS - biBC OR METASTASIS? a) METASTASES OF THE 1st BC b) DISTANT METASTASES c) METASTATIC TRACK BETWEEN BCs 1. DIFFERENT HISTOTYPES or 2. IN SITU COMPONENT IN THE 2nd BC or 3. BETTER DIFFERENTIATION IN THE 2nd BC or 4. “NO” VARIES AMONG HOSPITALS: biBC vs. monoBC:  biBC vs. monoBC NO DRASTIC DIFFERENCES: - AGE AT ONSET - TNM STATUS - MORPHOLOGY - FAMILY HISTORY - PROGNOSIS biBC vs. monoBC:  biBC vs. monoBC - NO DRASTIC DIFFERENCES IN THE AGE AT ONSET, TNM STATUS, MORPHOLOGY, FAMILY HISTORY, PROGNOSIS - TUMOUR NUMBER: 2 VS. 1 => - biBC PATIENTS HAVE VERY HIGH BC PREDISPOSITION (GENETIC OR NON-GENETIC) Slide6:  SOMATIC MUTATIONS IN BILATERAL BREAST CANCER 1. CONSISTENT WITH INDEPENDENT PRIMARY or METASTATIC ORIGIN? 2. SPECIFIC FEATURES of MOLECULAR PATHOGENESIS 3. if INDEPENDENT ORIGIN: CONCORDANCE or DISCORDANCE of SOMATIC MUTATIONS? Slide8:  Restoration of degraded DNA from archival paraffin-embedded tissues Slide9:  biBC: INDEPENDENT PRIMARY OR METASTATIC ? Allelotyping of tumor pairs (pattern of allelic losses and gains) - p53 mutations Slide10:  biBC allelotyping Slide11:  biBC: INDEPENDENT PRIMARY OR METASTATIC ? Very most if not all biBC are of biclonal origin => independent primaryies Slide12:  SOMATIC MUTATIONS IN BILATERAL BREAST CANCER 1. CONSISTENT WITH INDEPENDENT PRIMARY or METASTATIC ORIGIN? 2. SPECIFIC FEATURES of MOLECULAR PATHOGENESIS 3. if INDEPENDENT ORIGIN: CONCORDANCE or DISCORDANCE of SOMATIC MUTATIONS? Slide13:  Allelic imbalances and microsatellite shifts in biBC Microsatellite instability:  Microsatellite instability Mechanism: deficient mismatch repair Often in colon and endometrial cancers, never in breast cancer NB!!! Typical for treatment-induced tumors (chemo- or radio-) Slide15:  BAT26: reliable marker of microsatellite instability Microsatellite instability in biBC: frequent occurrence in metachronous contralateral tumors:  Microsatellite instability in biBC: frequent occurrence in metachronous contralateral tumors # 6/60 (10%) 2nd cancers from metachronous biBC pairs # 0/50 1st cancers from metachronous biBC pairs # 1/44 tumors from synchronous biBC pairs # 0/72 unilateral BC Slide17:  biBC: SPECIFIC FEATURES OF MOLECULAR PATHOGENESIS ? As many as 1 out of 10 contralateral metachronous BC seem to be induced by the treatment of the 1st tumor… Slide18:  SOMATIC MUTATIONS IN BILATERAL BREAST CANCER 1. CONSISTENT WITH INDEPENDENT PRIMARY or METASTATIC ORIGIN? 2. SPECIFIC FEATURES of MOLECULAR PATHOGENESIS 3. if INDEPENDENT ORIGIN: CONCORDANCE or DISCORDANCE of SOMATIC MUTATIONS? Slide19:  biBC allelotyping Slide20:  Concordance of allelic imbalances in synchronous and metachronous biBC Slide21:  “Classical” gene amplifications (ERBB2, C-MYC, cyclin D1) in 50 biBC pairs and 72 control unilateral BC Synchronous Metachronous Unilateral BC (control) B i l a t e r a l BC 1st 2nd Oncogene amplifications:  Oncogene amplifications Associated with poor prognosis Trend to concordance in synchronous biBC Depleted in 1st tumors from metachronous biBC pairs (Survival bias? Only patients with favorable (amplification-negative) 1st tumor have a chance to survive until 2nd BC) Slide23:  Molecular subtypes of breast cancer (expression arrays) Sorlie et al. (2001, 2003, 2006) van't Veer et al. (2002) Sotiriou et al. (2003) Perou et al. (2006) Luminal A Luminal B Basal-like ERBB2+ Normal-like Slide24:  Luminal A Luminal B Basal- like ERBB2 + Normal- like Estrogen receptor positive GATA3 LIV1 EMP2 Mucin 1 CCND1 XBP1 HMGCL CROT Keratin 8/18 DECR2 AR TFF1 ATP5G1 PRNPIP GGH LAMP4B PRDX4 SQLE Cyclin E Cadherin P CX3CL1 TRIM29 FZD7 Vimentin C-kit Keratin 5/17 Annexin 8 ADSL CD59 ERBB2 GRB7 TRAP100 FACL2 LPL AQP7 PIK3R1 Estrogen receptor negative Estrogen receptor positive Estrogen receptor negative Each BC subtype is characterized by expression of selected genes STAT1 IFI 1 Slide25:  Concordance of expression subtypes in synchronous biBC p = 0.05 Founder mutations in biBC:  Founder mutations in biBC BRCA1 5382insC: 14/140 (10%) CHEK2 1100delC: 6/119 (5%) NBS1 657del5: 2/173 (1.2%) 1/6 biBC: «founder» mutation Slide27:  Improved reliability of allele-specific PCR Conclusions (1):  Conclusions (1) Independent clonal origin of bilateral BC (not a metastasis to contralateral breast) As many as 10% second tumors from metachronous biBC pairs appear to be treatment-induced!!! Conclusions (2):  Conclusions (2) Similar molecular portraits of synchronous biBC (allelic imbalances, oncogene amplifications, expression profiles) Highly dissimilar portraits of metachronous biBC (survival bias: 1st tumors have favorable features; MSI in 2nd tumors) Slide31:  N.N. Petrov Institute of Oncology and Center of Mammology, St.-Petersburg: Molecular Biology: Evgeny Imyanitov, Alexandr Togo, Evgeny Suspitsin, Maxim Grigoriev, Ekaterina Kuligina, Evgeniya Belogubova, Konstantin Buslov, Julia Ulibina, Aglaya Iyevleva, Anna Sokolenko, Elena Chekmariova, Kaido Hanson; Morphology: Elena Leyenman, Elena Turkevich, Kazimir Pozharissky, Yulia Lazareva, Dmitry Matsko Patients Selection: Oleg Chagunava, Lev Berstein, Sergei Romanenko, Olga Ivanova, Vladimir Semiglazov CRLC, France: Carmen Rodriguez, Charles Theillet Norwegian Radium Hospital: Anne-Lise Borresen-Dale, Hege Giercsky Leiden University: Cees Cornelisse, Peter Devilee INTAS 03-4234: 12 articles in international journals

Add a comment

Related presentations

Related pages

Electricity of the Free Atmosphere: Amazon.de: I.M ...

I.M. Imyanitov - Electricity of the Free Atmosphere jetzt kaufen. ISBN: 9780706504750, Fremdsprachige Bücher - Fremdsprachige Bücher
Read more

Prof. Evgeny N. Imyanitov, author at LabTalk - the ...

Prof. Evgeny N. Imyanitov Head of research for tumour growth biology, N. N. Petrov Institute of Oncology, St. Petersburg, Russia. Prof. Evgeny N. Imyanitov ...
Read more

Naum S. Imyanitov - Citations

ResearchGate is a network dedicated to science and research. Connect, collaborate and discover scientific publications, jobs and conferences. All for free.
Read more

Ilya Imyanitov | Facebook

Ilya Imyanitov is on Facebook. Join Facebook to connect with Ilya Imyanitov and others you may know. Facebook gives people the power to share and makes...
Read more

Naum S. Imyanitov on ResearchGate

Naum S. Imyanitov is on ResearchGate. Read 31 publications, and contact Naum S. Imyanitov on ResearchGate, the professional network for scientists.
Read more

Anatoly Imyanitov | LinkedIn

View Anatoly Imyanitov’s professional profile on LinkedIn. LinkedIn is the world's largest business network, helping professionals like Anatoly Imyanitov ...
Read more

N. S. Imyanitov - academic.research.microsoft.com

Fields of study: Applied Chemistry, Inorganic Chemistry, Organic Chemistry. Sign in. Advanced ... N. S. Imyanitov,Applied Chemistry,Inorganic Chemistry ...
Read more

Identification of four novel susceptibility loci for ...

... Hooning MJ, Hoover RN, Hopper JL, Humphreys K, Hunter DJ, Huzarski T, Imyanitov EN, Isaacs C, Jakubowska A, James P, Janavicius R, Jensen UB, John ...
Read more

Ilya Imyanitov | LinkedIn

Ilya Imyanitov. Owner / Director of Business Operations at Dental Management Dynamics, LLC. Location Bensalem, Pennsylvania Industry Management Consulting
Read more

Concordance of allelic imbalance profiles in synchronous ...

Concordance of allelic imbalance profiles in synchronous and metachronous bilateral breast carcinomas. ... (Imyanitov et al.16 and unpublished data).
Read more