‫تقرير نهائي لمشروع بحث‬
Research project final report /
Rapport final du projet de recherche
‫مستند إداري‬
Administrative Document
--------
Administrative information / ‫المعلومات اإلداري‬
:‫المرجع‬
Project Title - )‫عنوان المشروع (عربي وأجنبي‬
BRAF Somatic Mutation in Primary and Metastatic Malignant Melanoma and
Melanocytic Nevi in Lebanon, Syria, Saudi Arabia and Pakistan
Principal Investigator - ‫الباحث الرئيسي‬
Room 340, 3rd floor, AUBMC, Cairo street, Beirut,
Lebanon
ik08@aub.edu.lb
‫العنوان‬
Ibrahim Khalifeh
Address
‫العنوان االلكتروني‬
e-mail
‫االسم والشهرة‬
Name &
surname
American University of
Beirut
‫المؤسسة‬
Institution
1
2014 ‫برنامج دعم البحوث العلمية‬
Grant Program for Scientific Research in Lebanon – 2014
Programme de subvention à la recherche scientifique au Liban – 2014
.1
‫رقم الهاتف‬
Associate Professor
Telephone
‫الوظيفة‬
Post
Co-investigators - ‫الباحثون المشاركون‬
‫العنوان االلكتروني‬
e-mail
rm11@aub.edu.lb
‫المؤسسة‬
Institution
American University of
Beirut
‫االسم والشهرة‬
Name and surname
Rami Mahfouz
Duration and starting date of the research / ‫المدة التعاقدي للمشروع وتاريخ بدء البحث‬
2 years
Duration (year) / ‫المدة التعاقدية للمشروع‬
June 2011
Starting date of the research /‫وتاريخ بدء البحث‬
Scientific Information / ‫العلمي‬
‫ المعلومات‬.2
ّ
Objectives - ‫الهدف‬
The aim of this study is to evaluate retrospectively the histological, clinical, and
molecular characteristics of melanocytic lesions in Lebanon, Syria, Saudi Arabia and
Pakistan. The material will be lumped into 3 regions according to sun exposure spectrum.
Group I will include the material coming from Syria and Lebanon. Group II will include
the material coming from Saudi Arabia. Group II will include the material coming from
Pakistan.
Achievements ‫أالنجازات المحقق‬
2
2014 ‫برنامج دعم البحوث العلمية‬
Grant Program for Scientific Research in Lebanon – 2014
Programme de subvention à la recherche scientifique au Liban – 2014


We have shown that BRAF mutational rate in primary melanomas from Near East
cohorts was intermediate between Eastern and Western cohort rates. We have also
obtained lower BRAF mutational rate with higher UV exposure rates for primary
and metastatic lesions. However, this may be due to other factors different from
potential UV exposure. Finally none of the studied morphologic parameters were
significant positive predictors of BRAF mutation.
The dysplastic nevi in our cohort show comparable size and demographics to what
was reported in other cohorts. The lesions were located predominately on the
trunk (72.8%), in keeping with the typical location of dysplastic nevi. The degree
of architectural disorder and cytological atypia were strongly proportional as
reported in other cohorts.29 However, based on the combined cytological and
architectural scores, the incidence of the degree of dysplasia showed a different
distribution, with more atypia reported in our cohort (mild: 19.2%, moderate: 48%
and severe: 32.8%) in comparison to a large homogenous Caucasian cohort (mild:
55.9%, moderate: 37% and severe: 7.1%).47 This illustrates potential geographic
differences in the distribution of degree of atypia with respect to dysplastic nevi.
In addition, our finding of significantly higher rates of pigment in the stratum
corneum of dysplastic nevi from Saudi Arabia may reflect an acquired protective
mechanism against the higher UV sun flux found in that geographic region.
Perspectives - ‫آفاق البحث‬



To study the demographics of BRAF mutations in dysplastic nevi of populations with differing
potential solar UV radiation exposure.
Study primary and metastatic melanomas from 2 ultraviolet radiation-distinct regions to elucidate
the correlation between prognostic predictors, ultraviolet radiation and BRAF mutation status.
Testing the BRAF status in matched primary and metastatic melanomas to optimize individual
targeted therapy.
Publications & Communications - ‫المنشورات والمساهمات في المؤتمرات‬
3
2014 ‫برنامج دعم البحوث العلمية‬
Grant Program for Scientific Research in Lebanon – 2014
Programme de subvention à la recherche scientifique au Liban – 2014



BRAF mutational epidemiology in dysplastic nevi: Does different solar UV radiation exposure
matter? (published)
BRAF Mutation Status in Primary and Metastatic Melanomas in Two Regions with Differing
Potential Ultraviolet Radiation Exposure (in press)
COMPARING BRAF MUTATION STATUS IN MATCHED PRIMARY AND METASTATIC
CUTANEOUS MELANOMAS: IMPLICATIONS ON OPTIMIZED TARGETED THERAPY
(under review)
Abstract - ‫موجز عن نتائج البحث‬
Cutaneous melanoma is the most serious form of skin cancer because it
metastasizes readily. Initially, it was regarded as a homogenous entity with uniform poor
prognosis, but the advent of specialized pigmented lesion clinics allowed detailed
multidisciplinary study of melanoma. As a result, a number of different subtypes with
distinct clincopathologic features have been described. More recently, molecular
differences among these subtypes have come to light, corroborating the clinicopathologic
observations.
Initial molecular studies have documented BRAF mutation in up to 66% of
melanomas. Subsequent studies have shown BRAF somatic mutations to be frequently
found in primary and metastatic melanomas and melanocytic nevi. The most common
BRAF mutation is the V600E alteration, but over 30 distinct BRAF mutations have been
found and may be predictive of clinically relevant tumor difference.
In melanoma cases, BRAF mutations are frequently found in superficial spreading
subtype, in tumors on intermittently sun-exposure sites and in younger patients. The exact
role of BRAF mutation in melanoma tumor progression, maintenance and outcome
remains controversial. Nonetheless, preclinical and early clinical studies predict that
BRAF pathway inhibitors may have therapeutic activity toward melanoma. Consequently
the tumor subclassification by BRAF mutation status may be necessary to evaluate their
efficacy.
BRAF somatic mutation in melanocytic lesions has not been studied in our region.
Nevertheless the demographics and epidemiology of BRAF mutations in different
population with diverse solar ultraviolet (UV) radiation due to climate regions has not
been investigated.
In this study, we aim to review retrospectively melanocytic lesions including
primary and metastatic melanomas and different types of melanocytic nevi in Lebanon,
Syria, Saudi Arabia and Pakistan. The study will have 3 major sectors: 1- Banal nevi
(intradermal, junctional, compound, spitz and blue nevi), 2- Dysplastic nevi and 3primary and metastatic melanomas. The geographic location, UV radiation, histologic
4
2014 ‫برنامج دعم البحوث العلمية‬
Grant Program for Scientific Research in Lebanon – 2014
Programme de subvention à la recherche scientifique au Liban – 2014
extent of UV damage, clinical features and histological parameters will be recorded in
every group in addition to BRAF mutation status. The results of every sector will be
tested against each of the other sectors to investigate any statistically significant
correlation.
‫توقيع الباحث‬
5
2014 ‫برنامج دعم البحوث العلمية‬
Grant Program for Scientific Research in Lebanon – 2014
Programme de subvention à la recherche scientifique au Liban – 2014