Mucinous ovarian cancer is distinct from extra-ovarian metastases and evolves from benign and borderline precursors.

Kylie L Gorringe

Group Leader (Junior Faculty)

Peter MacCallum Cancer Centre

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March 30 - April 2, 2014

Sheraton Sonoma County

Petaluma, California

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Where does MOC come from?Benign

Borderline

Extra-ovarian metastases

Low grade MOC

High grade MOC

Comparison with other tumour typesEvent

COAD ColonAdenocarcinoma 129

DSTAD DiffuseTypeStomachAdenocarcinoma 70

ECAD EndocervicalAdenocarcinoma 26

IHCH IntrahepaticCholangiocarcinoma 29

IPMN IntraductalPapillaryMucinousNeoplasm 8

MACR MucinousAdenocarcinomaColon/Rectum 23

MCN MucinousCysticNeoplasm 8

MSTAD MucinousStomachAdenocarcinoma 20

PAAD PancreaticAdenocarcinoma 258

PANET PancreaticNeuroendocrineTumor 98

PSC SerousCystadenomaofthePancreas 8

PSTAD PapillaryStomachAdenocarcinoma 6

READ RectalAdenocarcinoma 68

SOC SerousOvarianCancer 311

SPN PancreaticSolidPseudopapillaryNeoplasm 8

SSRCC StomachSignetRingCellCarcinoma 9

STAD StomachAdenocarcinoma 227

TSTAD TubularStomachAdenocarcinoma 61

UEC UterineEndometrioidCarcinoma 195

USC UterineSerousCarcinoma 43

APP Appendicealneoplasms 10-38*

BEN Benignmucinouscystadenoma 4-22*

BDL Borderlinemucinoustumour 30-44*

MOC Mucinousovariancarcinoma 195

Where does MOC come from?

BenignBorderline

Extra-ovarian metastases

Low grade MOC

High grade MOC

xWith expert pathology

Copy number burden crucial for progressionF

raction g

enom

e a

ltere

d b

y C

N

A

B C

Benign

Borderline

G1 MOC

G2 MOC

G3 MOC

Gain Loss

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 202122 X

BE

N

BD

L

G1

G2

G3

EO

M

EOM

G3

G2

G1

BDL

BEN

●●●

●

●

●

●

●

0.0

0.2

0.4

0.6

BEN BDL 1 2 3 EOM

Grade

FG

A

0 0.05 0.1 0.15 0.2

ValueP-value

Figure 2. CN analysis. A. Comparison of CN frequency across the genome, compar-

ing benign (BEN), borderline (BDL), MOC grade 1 (G1), grade 2 (G2) and grade 3

(G3) . B. Fraction of the genome altered (FGA) by group including extra-ovarian

(EOM) mucinous tumours (p<0.001). Tukey post-test comparison p-values shown at

right.C. Disease-specific survival by FGA. Score (logrank) test = 11.98 on 1 df,

p=0.002.

Dis

ease-s

pecific

surv

ival

BEN BDL G1 G2 G3

10%

Multivariate cox regression: p=0.011,

HR = 4.4, 95% CI 1.4-14(with stage, grade, ERBB2 amplification and 9p CN

loss; selected by AIC)

logrank P=4x10-5

Where does MOC come from?

BenignBorderline

Extra-ovarian metastases

Low grade MOC

High grade MOC

xWith expert pathology

Cell of origin??

AcknowledgementsCampbell/Gorringe Labs Pathology GAMuT - Australia

Ian Campbell Stephen Fox Westmead (NSW)

Dane Cheasley Prue Allan Anna deFazio

Simone Rowley Catherine Kennedy

Mei-Sim Lung GAMuT - Victoria Garvan (NSW)

Na Li WEHI Goli Samimi

Tanjina Kader Clare Scott Maret Boehm

Sakshi Mahale Matt Wakefield QIMR (QLD)

Hugo Saunders RMH/RWH Georgia Chenevix-Trench

Lisa Devereux Sumi Ananda

Georgina Bing Jan Pyman GAMuT - International

Abhimanyu Nigam Michael Christie Edinburgh (UK)

Carolina Salazar Alison Hadley Charlie Gourley

Former Orla McNally Michael Churchman

Sally Hunter Hudson Institute/Southern BCCA (Canada)

Georgie Ryland Andrew Stephens David Huntsman

David Choong Yoland Antill Jessica McAlpine

Michelle Torres Tom Jobling Blake Gilks

AOCS/CASCADE University of Calgary (Canada)

Bioinformatics David Bowtell Martin Koebel

Jason Li Nadia Traficante Mayo Clinic (US) Scott Kaufmann

Richard Lupat Sian Fereday Scott Kaufmann

Kaushalya Amarasinghe Joy Hendley COEUR tissue bank (Canada)

Niko Thio Kathryn Alsop

Magnus Zethoven Leanne Bowes

Genomics Core

Gisela Mir-Arnau

Gain

Loss

Chromosome

BEN (22)

BDL (39)

G1 (87)

G2 (81)

G3 (24)

A

B C

Benign

Borderline

G1 MOC

G2 MOC

G3 MOC

Gain Loss

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 202122 X

BE

N

BD

L

G1

G2

G3

EO

M

EOM

G3

G2

G1

BDL

BEN

●●●

●

●

●

●

●

0.0

0.2

0.4

0.6

BEN BDL 1 2 3 EOM

Grade

FG

A

0 0.05 0.1 0.15 0.2

ValueP-value

Figure 2. CN analysis. A. Comparison of CN frequency across the genome, compar-

ing benign (BEN), borderline (BDL), MOC grade 1 (G1), grade 2 (G2) and grade 3

(G3) . B. Fraction of the genome altered (FGA) by group including extra-ovarian

(EOM) mucinous tumours (p<0.001). Tukey post-test comparison p-values shown at

right.C. Disease-specific survival by FGA. Score (logrank) test = 11.98 on 1 df,

p=0.002.

Progression from borderline to grade 3 metastatic

P=2x10-9 P=8x10-7