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Asthma & allergy sig: poster session 1 - airway inflammation and allergy

Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-110
LUNG CANCER WAITING TIMES AT THE ROYAL ADELAIDE HOSPITAL
BD DOUGHERTY, PC ROBINSON, M OBORN
Department of Thoracic Medicine, Royal Adelaide Hospital, SA 5000

Introduction: Waiting times for cancer diagnosis and treatment are
monitored and published in the United Kingdom (UK).We undertook an
audit to determine the performance of the Royal Adelaide Hospital (RAH) in
diagnosis, staging and commencing treatment of lung cancer patients.
Methods: We retrospectively identified 100 patients referred to the RAH
between February and September 2010 with histologically confirmed lung
cancer. Case note review identified key dates in diagnosis and treatment.
We calculated mean time intervals between these points.
Results: Complete data was available for 87 patients. The average time
from GP referral to 1st appointment was 10.08 days. The average time to
histological diagnosis was 11.5 days. The waiting time for a bronchoscopy
was 4.28 days, for CT-FNA 10.4 days, EBUS-TBNA 11.8 days, a PET scan
14.2 days, and lung function 8.83 days. Patients waited a 7.3 days for a
second appointment. A surgical OPD took 24.79 days from diagnosis, then
46.36 days to actual surgery. Medical oncology clinic from diagnosis took
28.83 days, chemotherapy started 29 days after this. Radiation oncology
appointments 24.2 days, radiotherapy started 22.54 days thereafter.
Discussion: The National Health Service in the UK sets 3 cancer waiting
times targets : (1)all suspected cancers be seen by a specialist within 14
days of GP referral ; (2)treatment begins within 31 days of diagnosis ;
(3)treatment begins within 62 days of GP referral. The RAH achieved the
first target in 10.08 days, but treatment from diagnosis took 58.5 days, and
from GP referral took 80 days in our cohort.
Conclusion:There are delays in the diagnosis and treatment of lung
cancer patients at the RAH when compared to UK targets.
Conflict of interest no
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-111
TRENDS IN CHARACTERISTICS OF PATIENTS WITH PRIMARY LUNG
CANCER, A RETROSPECTIVE COHORT REVIEW 1998 – 2010.
CLAIRE M. ELLENDER, MARGARET DAUTH AND MICHELLE MURPHY
Department of Respiratory Medicine, Princess Alexandra Hospital,
Woolloongabba, QLD 4102

Patients seen at Princess Alexandra Hospital (PAH) with thoracic
malignancies have been registered in a centralised database since 1998.
This study assessed the characteristics and outcomes of patients at PAH
with primary lung cancer.
Method: A retrospective cohort analysis of patients diagnosed with primary
lung cancer 1998 to 2010 was performed. Characteristics such as age,
gender, presenting complaint, co-morbidities, histology, stage, sites of
metastatic disease and survival were reviewed.
Results: The total number of cases of primary lung cancer presenting to
PAH increased by over the study period (167 to 295) with an annual growth
rate of a 6%. Age at presentation has remained stable over time; the most
common age was 60 – 69 years. The proportion of women increased from
30% to 41%. The most common presenting complaints were cough (46%),
dyspnoea (45%) and weight loss (39%). Patients with primary lung cancer
had multiple co-morbidities, such as cardiovascular disease (51%) and
COPD (39%). Non small cell lung cancer (NSCLC) represented 79% of
cases, small cell lung cancer (SCLC) 16%, mesothelioma 4% and carcinoid
1%. Overall, 39% of patients with NSCLC were Stage 4 at diagnosis, with
the proportion of Stage 4 cases increasing over time. The ratio of Extensive
Stage to Limited Stage SCLC changed over time, with Extensive Stage
becoming more common. The most frequent sites of metastatic disease
were bone (11%), lung (10%), liver (8%) and brain (8%). NSCLC mortality
varied with Stage and improved over time. The average 5 year survival
(5YS) was: Stage 1 29%, Stage 2 32%, Stage 3A 9%, Stage 3B 9% and
Stage 4 5%. The average 5YS for patients with Limited Stage SCLC was
15% and 2% for Extensive Stage.
Conclusions: The number of patients presenting to PAH with primary lung
cancer is growing. Unfortunately, the proportion of patients with Stage 4
NSCLC is increasing. Survival outcomes remain poor for all Stages of
disease.
Keywords: primary lung cancer, trends, staging, survival
Conflict of interest No
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-112
LUNG CANCER PATHWAY FROM INITIAL PRESENTATION TO
DIAGNOSIS IN TWO CENTRES IN NEW ZEALAND

W
, CA LEWIS , G STEVENS , JE GARRETT , J KOLBE 1Department of Medicine, University of Auckland; 2 Northern Cancer
Network; 3 Respiratory Services, Auckland District Health Board;
4Respiratory Services, Counties Manukau District Health Board, Auckland,
NZ
Background A previous Auckland audit of lung cancer care in 2004
identified that patients are more often diagnosed with lung cancer only at
the time of an acute admission and often with advanced disease, rather
than as a consequence of primary care referral to outpatient services.
Aim To re-evaluate the presentation of lung cancer in a 2008 cohort, to
compare presentation between metropolitan and regional settings, and to
evaluate events within primary care prior to diagnosis.
Methods Cases from 2008 were identified from the NZ Cancer Registry
and databases of participating primary care organisations within the
Auckland and Lakes regions. Data was collated from primary and
secondary care records.
Results There were 272 eligible cases. Mean age was 68yrs; 50% were
female; 10% were never-smokers. Three-quarters of cases presented
initially to primary care (PC) and one-quarter presented directly to
secondary care (SC). Median time to diagnosis from PC presentation was
65 days (IQR 31;123) compared with 17 days (8;45) from direct SC
presentation. Only 26% of PC cases were initially referred to an outpatient
respiratory specialist; whereas 44% presented acutely to SC (23% GP-
referred; 21% self-referred). Chest Xray was performed in patients
presenting to PC in 65% of cases, and 11% had a CT ordered in PC;
spirometry was documented within PC records in 36% of cases.
Conclusions Patients with lung cancer commonly present with advanced
disease, requiring admission either as a consequence of self referral or GP
referral. Patients presenting via PC are more likely to have earlier stage
disease but take longer to achieve diagnosis. Strategies are needed to
promote earlier recognition and presentation of lung cancer, and expedite
diagnosis in the outpatient setting.
Supported by: Health Research Council of New Zealand
Conflict of interest
No
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-113
PHYSIOTHERAPY PRACTICE PATTERNS FOR PATIENTS
UNDERGOING SURGERY FOR LUNG CANCER – PRELIMINARY
RESULTS
V C
AVALHERI,1 S JENKINS,1,2,3 K HILL 1 School of Physiotherapy and Curtin Health Innovation Research Institute,
Curtin University, WA 6845 2Lung Institute of Western Australia, Sir
Charles Gairdner Hospital, WA 6009 3Physiotherapy Department, Sir
Charles Gairdner Hospital, WA 6009
Introduction: There has been a recent increase in the research available
to guide physiotherapists regarding the management of patients who
require surgical resection for lung cancer. However, it is unclear whether
this evidence has influenced clinical practice. The aim of this study was to
describe physiotherapy practice patterns in the pre- and post-operative
management of patients who require surgical resection for lung cancer.
Methods: Physiotherapists involved in the management of patients who
require surgical resection for lung cancer, at hospitals across Australia and
New Zealand, were mailed a purpose-designed questionnaire.
Results: To date, of the 45 questionnaires distributed, 21 (47%)
questionnaires have been returned. Prior to surgery, patients in the majority
of hospitals are assessed by a physiotherapist (n=12; 57%), but do not
participate in supervised exercise training (n=19; 90%). Most commonly,
physiotherapy is commenced on the day following surgery (n=19; 90%) with
walking-based exercise being the most frequent treatment undertaken (n
=19; 90%). Fifty-seven per cent of respondents refer less than 25% of
patients to pulmonary rehabilitation on discharge from hospital.
Physiotherapy practice is influenced predominantly by established practice
in the hospital and personal experience, and not by research findings.
Conclusion: Physiotherapy services focus on the acute post-operative
management of patients following surgery for lung cancer. Despite recent
data suggesting exercise training is beneficial in this population, our data
indicate that referral to pulmonary rehabilitation is uncommon for this
patient population.
Nomination: Physiotherapy Prize.
Supported by:Curtin Strategic International Research Scholarship
(CSIRS).
Conflict of Interest: No
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-114
BEWARE B-DUMP: A RARE PARANEOPLASTIC SYNDROME
MI BIRADER, BD DOUGHERTY
Department of Thoracic Medicine, Royal Adelaide Hospital, SA 5000

Introduction: Clues to respiratory diagnoses can lie outside of the
respiratory system. We present a case of lung cancer where unilateral
visual loss was the only symptom, and review the literature around Bilateral
diffuse uveal melanocytic proliferation (BDUMP) syndrome.
Case Presentation: 72/male, retired miner from Broken Hill, NSW, 40 pack
year smoking, presented with sudden onset painless visual loss in the right
eye. On examination palpable right supraclavicular (SC) fossa node,
inflamed right eye anterior segment, visual acuity 6/36 right / 6/9 left
.Normal cardio respiratory system. Initially diagnosed as anterior ischaemic
optic neuropathy; a lesion in the iris was suspected to be an incidental
ocular melanoma. A temporal artery biopsy was negative for temporal
arteritis. CT Chest to look for melanoma metastases showed a left lower
lobe (LLL) 7.5 cm mass, with bulky mediastinal and hilar lymphadenopathy.
Bronchoscopy revealed an obstructed LLL bronchus, and histology showed
adenocarcinoma (TTF-1 positive). Mass and right SC lymph node was FDG
avid on PET scan; FNAC of the node showed TTF-1 positive
adenocarcinoma. Ophthalmologic examination revealed bilateral uveal
changes, and diagnosis of BDUMP syndrome was made. This upstaged the
lung cancer from 3B to 4 and patient received palliative radiotherapy and
subsequent palliative chemotherapy.
Discussion: BDUMP is a rare paraneoplastic syndrome first described in
1966. Typical ocular changes are of progressive visual loss, with multiple
red patches on the retinal pigment epithelium, development of melanocytic
tumors and thickening of the uveal tract, conjunctival hyperemia and uveitis.
It is most closely associated with gynecological malignancy in women and
lung cancer in men but has also been associated with colon, pancreas,
gallbladder, breast and esophageal cancer.
Conflict of interest: No
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-115
DISCOVERY OF NEW ACTIVE DRUGS FOR TREATMENT OF
MALIGNANT MESOTHELIOMA BY SCREENING THE JHCCL CLINICAL
COMPOUND LIBRARY.
V
, J SCHAGEN , L MORRISON , J MARTINS , BE CLARKE , 1 Department of Thoracic Medicine, The Prince Charles Hospital, 2 School
of Medicine, The University of Queensland, Brisbane, Australia
Background: Australia has the highest reported incidence of malignant
mesothelioma in the world. There is currently no highly effective therapy.
Aim: We aimed to discover new drugs for treatment of MM by screening a
library of compounds already approved for clinical use (Johns Hopkins
Clinical Compound Library-JHCCL).
Material and Methods: A panel of 7 mesothelioma cell lines were
screened against 1524 JHCCL compounds using a growth inhibition assay
with SYBR(R) Green I- fluorometric readout.
Results:
At a final concentration of 10μM, 148 drugs produced at least
50% growth inhibition on all seven cell lines. Of these active compounds,
61 had a history of oral or parenteral clinical use and 38 of these have been
retested in dose response experiments at final concentrations ranging from
100µM to 0.01µM to date. 50% growth inhibitory concentrations (IC50)
confirmed the in vitro anti-mesothelioma activity of 27 of 38 compounds
with IC50s ranging from 0.02µM – 130µM. 2 of 10 compounds IC50
concentrations were equal to published peak plasma concentrations.
Conclusions: Compounds with in vitro anti-mesothelioma activity were
identified from a panel of agents with a prior history of clinical use. The
anti-mesothelioma activity now requires validation in vivo or in clinical
settings.
Acknowledgements: Cancer Australia, Dust Disease Board and The
Prince Charles Hospital Foundation.
Nomination: Slater and Gordon International Mesothelioma Travel Grant
2012, TSANZ Travel Grants to the 2012 ASM
Conflict of Interest: None
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-116
CHANGING PATTERN OF OCCUPATIONAL ASBESTOS EXPOSURE IN
PEOPLE WITH MALIGNANT MESOTHELIOMA IN WEST AUSTRALIA
AW
, N OLSEN , K SHILKIN , T THRELFALL , A REID , E LEE , 1Sir Charles Gairdner Hospital, West Australia; 2School of Population
Health, 3School of Pathology & Laboratory Medicine, 4Centre for Medical
Research, 5Centre for Child Health Research, University of West Australia,
6Cancer Registry, Dept of Health, West Australia.

Introduction: The WA Mesothelioma Registry has documented every case
of malignant mesothelioma (MM) in WA since the first case in 1962. Cases
attributed to domestic exposures have increased. (MJA 2011;195:271).
Aim: To investigate the patterns of occupational asbestos exposure
associated with MM over the past 50 years in WA.
Methods: All MM cases are reviewed and confirmed by an expert
committee. The source of asbestos exposure most likely to have been
responsible for the disease is determined from all clinical information. 19
categories of occupational exposure were considered. The % of cases per
category for each decade was calculated.
Results: There were 1723 cases of MM between 1962 and 2009: 1263
(1226 males) were attributed to occupational exposure. Numbers have
reached a plateau in the last 10 years (55 – 65 annually). Cases attributed
to work at the Wittenoom crocidolite mine to 1966, have remained constant
but decreased as a % of all cases. Cases attributed to exposure in
asbestos transport, the armed forces, asbestos cement production, the
waterfront, ship building and in insulation workers peaked by 2000 but
cases in construction workers, electricians and boilermaker/welders have
increased in number. There have been 3 cases in non-asbestos miners.
Conclusion: This data shows declining proportions of first and most
second wave cases. There has been little evidence of cases associated
with the extensive amount of mining of other minerals in WA.
Supported by: NHMRC Australia
Conflict of Interest: Nil
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-117
EFFECT OF RADIOGRAPHIC ABNORMALITIES ON MENTAL HEALTH
OF WORKERS AND RESIDENTS OF WITTENOOM, WESTERN
AUSTRALIA
P
ABOAGYE-SARFO , P FRANKLIN , A REID , N DE KLERK , N OLSEN , 1 School of Population Health, The University of Western Australia, 2 Sir
Charles Gairdner Hospital, Nedlands, Western Australia, WA 6009

Introduction: Exposure to asbestos causes radiographic abnormalities
such as pleural plaque (PP), diffuse pleural thickening (DPT) and
asbestosis. Knowledge of presence of these radiographic abnormalities
may affect individuals’ mental health (MH).
Aim: To examine the effect of radiographic abnormalities on the MH of
people exposed to crocidolite.
Subjects: Subjects are former workers and residents of Wittenoom, a
crocidolite mining town in Western Australia, who had participated in a
program of annual health review.
Methods: The diagnosis of PP, DPT or asbestosis was determined from
plain chest x-rays read by 2 observers according to the ILO classification of
radiographs for the pneumoconiosis. In 2007 participants had completed a
questionnaire that included questions on mental health status (SF-12) and
sense of personal control (SOPC). Generalised linear modelling was used
to relate the presence of PP, DPT and asbestosis to MH scores and SOPC
scores controlling for asbestos exposure measurements, smoking status,
other cancers, general physical health and demographic variables.
Results: A diagnosis of asbestosis was significantly associated with worse
MH status ( = -0.04; 95% CI: -0.079 -0.004; p=0.031) but not SOPC. The
presence of PP and DPT were not related to either poor mental health or
reduced SOPC.
Conclusion: The presence of PP or DPT, in the absence of other disease,
does not affect the mental health of crocidolite exposed subjects from
Wittenoom. However, patients with asbestosis have evidence of worse MH
compared to other asbestos exposed individuals.
Supported by: NHMRC Australia
Conflict of Interest: No
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session TP-119 AUSTRALIAN MESOTHELIOMA REGISTRY P LAWS , L HUANG , A RAFTERY , MR SIM , W MUSK , A ANDERSON , J HILL , 1Cancer Institute NSW; 2Monash University Centre for Occupational and Environmental Health; 3Western Australian Mesothelioma Registry; 4Safe Work Australia; 5Cancer Epidemiology and Health Services Research Group, University of Sydney; 6Asbestos Diseases Research Institute Introduction: Australia has a legacy of a large amount of asbestos in
buildings and other infrastructure and a high incidence of malignant
mesothelioma. Due to the long latency between exposure to asbestos and
the onset of mesothelioma, incidence is probably yet to peak. The
Australian Mesothelioma Registry (AMR) collects information on all new
cases, including detailed information on asbestos exposure.
Methods: The AMR is funded by Safe Work Australia and managed by
Cancer Institute NSW, who coordinate notifications from state/territory
cancer registries. Participants are assessed for past asbestos exposure by
the Monash Centre for Occupational and Environmental Health. Hunter
Valley Research Foundation conducts telephone interviews. Clinician
involvement is required to provide advice about eligibility of patients for
recruitment to the asbestos exposure component of the AMR, which
involves the patient completing a postal questionnaire and telephone
interview. If clinicians do not respond to AMR requests, detailed information
on occupational and environmental asbestos exposure cannot be obtained.
Results: The AMR became operational in 2011. It is expected that around
700 cases of mesothelioma will be notified to the Registry in the first year,
and this number is expected to increase over coming years. Exposure
assessments will provide detailed information not previously available.
Conclusions: AMR information will aid federal and state governments to
develop policies to deal with asbestos in buildings and other infrastructure.
It provides a national resource for researchers to identify preventable risk
factors to assist in reducing mesothelioma in the future.
Conflict of Interest:
No
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-120
CORRELATES OF WHEEZE AND COUGH AND PHLEGM AMONG
BUSSELTON ADULTS
J
, MW KNUIMAN , ML DIVITINI , M HUNTER , 1 Busselton Population Medical Research Institute, 2Pathwest Laboratory
Medicine, 3Dept of Pulmonary Physiology and Sleep Medicine/West
Australian Sleep Disorders Research Institute, 4Dept of Respiratory
Medicine and; 5School of Population Health and 6School of Medicine and
Pharmacology, University of Western Australia, Crawley, Western
Australia.

Aim To examine correlates of wheeze (W) and cough/phlegm (C/P) in a
general population.
Subjects 2,645 adult participants in the 2005-7 Busselton health survey.
Methods Logistic regression was used to assess associations after age
and gender adjustment.
Results The prevalence of W was 52% in women and 48% in men. Mean
BMI and waist circumference were 26.6 kg/m2 and 90.2cms in people with
no W or C/P and 27.7, 93.2; 27.3, 93.6 and 28.3cms, 96.6 kg/m2 in people
with W only, C/P only or W and C/P respectively. Both W and C/P (alone
or together) were associated with reflux, current smoking and dusty job and
were more common in people with both W and C/P. Lung function (LF)
(OR 0.67; 95% CI 0.57-0.78), eNO (OR 1.18; 1.08-1.40), atopy (OR 1.96;
1.37-2.79), ex and current smoking (OR 1.53, 1.65; 1.06-2.22, 1.01-2.69)
and feathers in bedding (OR 1.54; 1.06-2.24) were significant
discriminators of W vs C/P.
Conclusions Both W and C/P (alone or together) are associated with
increased BMI and waist circumference. Reflux, LF, eNO, atopy, BMI and
smoking are independently related to W while reflux, LF, smoking and
dusty job are independently related to C/P. People are more likely to have
W if they are female, < 40 years, have lower % pred FEV1, higher % pred
FVC and have atopy. LF and atopy are best for discriminating between
people who have W only or C/P only.
Supported by: NHMRC Grant 353532
Nomination: No
Conflict of interest: No
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-121
THE PREVALENCE OF RESPIRATORY CONDITIONS IN “BABY-
BOOMERS” – THE BUSSELTON HEALTHY AGEING STUDY
ML
1Busselton Population Medical Research Institute, 2 West Australian Sleep
Disorders Research Institute, 4Respiratory Medicine and 5Pathwest
Laboratory Medicine, Sir Charles Gairdner Hospital, WA, Australia, 6School
of Population Health and 3School of Medicine and Pharmacology,
University of Western Australia, WA, Australia

Aim To estimate the prevalence of respiratory il ness in up to 3500 “Baby
Boomers” (born 1946-1964) randomly sampled from the Shire of Busselton
as part of a comprehensive health survey including respiratory, allergy and
sleep disorders, cardiovascular disease, muscle strength and physical
function, obesity, diabetes, vision and hearing, bone density, spinal pain,
mental health and cognition.
Methods Respiratory and allergy information was collected using
standardised questionnaires, pre and post-bronchodilator spirometry, two-
channel sleep studies and skin prick responses to common aero-allergens.
Results The prevalence of doctor-diagnosed respiratory conditions among
the first 205 attendees (mean age 55.8 years, 56% women) were higher in
women than men for asthma (17% vs 14%), bronchitis (19% vs 6%),
hayfever (32% vs 21%), pneumonia (10% vs 6%), pleurisy (9% vs 2%) and
sinusitis (22% vs 9%). Respiratory symptoms including wheeze or chest-
tightness (ever or within the last 12 months) were also more common in
women. Current tobacco smoking (12% vs 3%), atopy (46% vs 44%), sleep
apnoea (15% vs 5%), objective measures of airway obstruction (FEV1
<80%, 12% vs 5% or FEV1/FVC Ratio <70%, 19% vs 10%) and
unambiguous bronchodilator response (>12% increase in FEV1 post-
salbutamol, 5% vs 3%) were more prevalent in men than women.
Conclusion While women “Baby-Boomers” more often report respiratory
symptoms and a history of respiratory conditions, men had lower levels of
lung function and higher levels of allergy and sleep apnoea.
Supported by: Department of Commerce, Government of WA, Shire of
Busselton.
Nomination: None
Conflict of interest:
No
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-122
SURVIVAL OF A PATIENT WITH DISSEMINATED MICROSPORIDIOSIS
WITH PULMONARY INVOLVEMENT FOLLOWING RENAL TRANSPLANT
S KARUNARATHNE, H GREVILLE, P REYNOLDS
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide. SA
5000
We report a very rare case of disseminated microsporidiosis with
pulmonary involvement in a renal transplant patient.
The patient had a cadaveric renal transplant in April 2010 because of
diabetic nephropathy. He presented with respiratory failure in June 2011
and was admitted to intensive care unit where he required intubation and
ventilation. He was treated with broad spectrum antibiotics, anti fungal and
anti viral medications for 2 weeks without any clinical improvement. A renal
biopsy showed microsporidia spores. Subsequent modified Trichrome
stains of Bronchoalveolar lavage, Sputum and Urine showed microsporidia.
DNA polymerase chain reaction analysis and electron microscopy
confirmed the diagnosis. Patient was treated with oral Albendazole 400mg
twice daily. He had a marked clinical and radiological improvement over the
ensuing 3 weeks. Microsporidia are intracellular spore forming parasites
classified as fungi. Microsporidia can be highly pathogenic in humans.
Encephalitozoon cuniculi species usually cause disseminated infection but
intestinal infection is rare. Albendazole has demonstrated activity against
Encephalitozoon cuniculi in vitro. While the majority of cases of invasive
microsporidiasis have been documented in patients with HIV/AIDS invasive
microsporidiasis has been reported in solid organ transplant patients.
Conclusion Microsporidia should be considered as a part of the
differentiated diagnosis of pulmonary infections in immunosuppressed
patients who are not responding to the usual antiinfective agents. A high
level of clinical suspicion is needed and a close collaboration with the
microbiology lab is required to establish the diagnosis.
Conflict of interest None
Combined Lung CancerSIG and OELD & Population Health SIG: Poster Session
TP-123
ABSENCE OF MUTATIONS IN HEDGEHOG PATHWAY GENES PTCH1
AND SMO IN MALIGNANT MESOTHELIOMA CELLS
CB
, HM CHEAH , S BALTIC, PJ THOMPSON , CM PRÊLE 1Lung Institute of Western Australia and 2Centre for Asthma, Allergy and
Respiratory Research, University of Western Australia, Perth, WA

Aim To determine whether the Hedgehog (HH) pathway is aberrantly
activated in malignant mesothelioma (MM) and assess whether mutations
in PTCH1 and SMO are responsible for pathway activation.
Methods Activation of the HH pathway in 6 human MM cell lines was
determined by measuring mRNA levels of the downstream effectors GLI1
and GLI2. Exonic sequencing of PTCH1 and SMO from these cell lines was
performed. All mutations found were confirmed by an independent PCR
and sequencing. SIFT program was used to predict the likelihood that an
amino acid substitution would have a phenotypic effect.
Results Hyperactivation of the pathway was observed in all cell lines
except JU77. No substitution mutations in PTCH1 and SMO were detected
in the coding region of PTCH1 and SMO. However, several previously
reported SNPs were identified. Exons 18,19,20,21,22 and 23 of PTCH1
were deleted. In addition, we also identified a 3bp insertion repeat in LO68
cell line.
Conclusions
Our data indicate that in MM, hyperactivation of the HH
pathway does not involve substitution mutations in the coding region of
PTCH1 and SMO. Although it is to be confirmed, it is unlikely that neither
the SNPs nor the trinucleotide repeat insertion are responsible for
hyperactivation of the pathway.
Supported by National Health and Medical Research Council and
International Mesothelioma Applied Research Foundation
Nomination
Conflict of Interest
No

Source: http://anzsrs.rewarddesign.net/23.pdf

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