imyanitov

Information about imyanitov

Published on February 28, 2008

Author: Maurizio

Source: authorstream.com

Content

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

Related presentations


Other presentations created by Maurizio

Lecture 13
08. 01. 2008
0 views

Lecture 13

Rona Grimmer Grampian Police
09. 01. 2008
0 views

Rona Grimmer Grampian Police

experimental prob
10. 01. 2008
0 views

experimental prob

The Marble Champ
10. 01. 2008
0 views

The Marble Champ

3 RogerBanks ITC
10. 01. 2008
0 views

3 RogerBanks ITC

Passive Voice and Adverbs
14. 01. 2008
0 views

Passive Voice and Adverbs

lin3
15. 01. 2008
0 views

lin3

powerpoint sample
15. 01. 2008
0 views

powerpoint sample

chapter8
16. 01. 2008
0 views

chapter8

photometry
16. 01. 2008
0 views

photometry

macbethact2
21. 01. 2008
0 views

macbethact2

textile
22. 01. 2008
0 views

textile

BiofuelsJuly2006shor tv2
22. 01. 2008
0 views

BiofuelsJuly2006shor tv2

Stroke 06 001
04. 02. 2008
0 views

Stroke 06 001

Achieving Wireless
04. 02. 2008
0 views

Achieving Wireless

sargam poster
15. 01. 2008
0 views

sargam poster

IST 200701
06. 02. 2008
0 views

IST 200701

PRMs 02 11
18. 02. 2008
0 views

PRMs 02 11

Main presentation
20. 02. 2008
0 views

Main presentation

0 Introduction
16. 01. 2008
0 views

0 Introduction

leFriant Chris
20. 01. 2008
0 views

leFriant Chris

Lecture 29 SPT DEC
21. 01. 2008
0 views

Lecture 29 SPT DEC

ActuarialProfession0 607
14. 03. 2008
0 views

ActuarialProfession0 607

20 3 Vertebrates form function
19. 03. 2008
0 views

20 3 Vertebrates form function

maynews
03. 04. 2008
0 views

maynews

Lecture22 LargeSatsII
13. 02. 2008
0 views

Lecture22 LargeSatsII

Worldmapper presentation small
28. 03. 2008
0 views

Worldmapper presentation small

safety presentation
05. 02. 2008
0 views

safety presentation

rcdt 061127 04
16. 04. 2008
0 views

rcdt 061127 04

Kickoff Poster Brazil
22. 01. 2008
0 views

Kickoff Poster Brazil

PHED190sportpsycholo gy
17. 04. 2008
0 views

PHED190sportpsycholo gy

speech final Macau
23. 04. 2008
0 views

speech final Macau

The Big Hope march 08
24. 04. 2008
0 views

The Big Hope march 08

PRE DOHA REV
07. 05. 2008
0 views

PRE DOHA REV

2007531101543139
02. 05. 2008
0 views

2007531101543139

BP Idol
10. 01. 2008
0 views

BP Idol

AC2007KhanLecture
05. 03. 2008
0 views

AC2007KhanLecture

LandTour05
25. 02. 2008
0 views

LandTour05

RO CLIL
17. 01. 2008
0 views

RO CLIL

David Brock NASA MSFC
13. 01. 2008
0 views

David Brock NASA MSFC

cfg07 quiz
04. 02. 2008
0 views

cfg07 quiz

133 2005ss elisagaleotti2
11. 01. 2008
0 views

133 2005ss elisagaleotti2