| Abstract | CILJ ISTRAŽIVANJA: Mutacije BRCA1 i BRCA2 gena su poznati čimbenici rizika za
nastanak raka dojke i jajnika. Spektar BRCA1/2 mutacija u bolesnica sa seroznim karcinomom
jajnika visokog gradusa u Hrvatskoj još nije opisan. Ovakve izvješća su važna za optimizaciju
genetskog testiranja, strategiju primarne i sekundarne prevencije te za individualizaciju
liječenja naših pacijenata s rakom jajnika.
ISPITANICE I METODE: Retrospektivno su analizirani podaci iz povijesti bolesti 55
bolesnica s BRCA mutiranim, seroznim, visoko-gradusnim karcinomom jajnika liječenih i
praćenih na Odjelu za onkologiju i radioterapiju u Splitu. Prikupljeni podaci uključivali su dob
bolesnika u trenutku dijagnoze, obiteljsko opterećenje sa zloćudnim bolestima, primarno sijelo
bolesti, histološki podtip, stadij bolesti, BRCA status, vrste BRCA mutacija, značajke
kirurškog i onkološkog liječenja, te specifičnosti metakronih i sinkronih karcinoma u bolesnika
s BRCAm karcinomom jajnika.
REZULTATI: Analizirano je 55 pacijentica s novodijagnosticiranim i/ili rekurentnim
BRCAm seroznim, visoko-gradusnim rakom jajnika. Medijan životne dobi u trenutku
dijagnoze bolesti bio je 54 godine (raspon 36-76). Otkrili smo 37 pacijenata s mutacijama
BRCA1 (67%) i 18 pacijenata s mutacijama BRCA2 gena (33%). Prosječna dob bolesnica za
BRCA1m bila je 52 godine (raspon 36-76), a za BRCA2m 56 godina (raspon 47-68). Među
BRCA1 mutacijama najčešće su otkrivene mutacije c.5266dup u 18 bolesnika (32,7%) i
c.1252G>T u 8 bolesnika (14,5%). OstaleBRCA1m otkrivene u 2 bolesnice bile su c.4113delG
i c.843-846del, te u 1 bolesnice: c.3342del, c.5409>A, c.181T>G, c.3343del, c.4356del,
c.5503C> T i c.1508del. Dvije najčešće BRCA2m prisutne u našoj populaciji bile su c.6641dup
(5 bolesnika, 9%) i c.9371A>T (3 bolesnika, 6%). Ostale BRCA2m otkrivene u 2 bolesnice
bile su c.5073dupA i c.8331+1G>T, te u 1 bolesnice: c.6486_6489del, c.4593del, 3663del,
c.4563_4564del, c.6037A>T i c.9286G>T.
ZAKLJUČAK: Najčešća mutacija BRCA1 gena u našoj studiji (c.5266dup, p.Gln1756fs) je
najčešća mutacija u stanovnika slavenskih zemalja kao što su Rusija, Bjelorusija, Poljska,
Češka, Slovenija, te u sjevernoj Grčkoj, druga po učestalosti u aškenaskoj židovskoj populaciji,
a treća po učestalosti u zemljama sjeverne Afrike (Maroko, Alžir i Tunis). |
| Abstract (english) | OBJECTIVE: Mutations in BRCA1 and BRCA2 are well-established risk factor for breast
and ovarian cancer. The spectrum of BRCA1/2 mutations in high grade serous ovarian cancer
patients have not yet been fully described in Croatia. These observations may be important to
optimize the genetic testing, primary and secondary prevention strategies and individualize
treatment for our ovarian cancer patients.
PATIENTS AND METHODS: Data from the medical history of 55 patients with BRCAm
high grade serous ovarian cancer treated and followed at the Department of Oncology and
Radiotherapy in Split were retrospectively analyzed. Data included age of patient at diagnosis,
family history of malignancies, primary disease, histological subtype, stage of disease, BRCA
status, spectrum of BRCA mutations, features of surgical and oncological treatment, specific
of metachronous and synchronous cancers in patients with BRCAm ovarian cancer.
RESULTS: We have analyzed 55 patients with newly diagnosed and/or recurrent BRCAm
high grade serous ovarian cancer. The median age of diagnosis was 54 years (range 36-76). We
detected 37 patients with BRCA1m (67%) and 18 patients with BRCA2m (33%). The median
age of diagnosis for BRCA1m patients was 52 years (range 36-76), and for BRCA2m patients
56 years (range 47-68). Among those with BRCA1m, the most frequently detected mutations
were c.5266dup in 18 patients (32,7%) and c.1252G>T in 8 patients (14,5%). Other BRCA1m
detected in 2 patients were c.4113del and c.843-846del and in 1 patient were c.3342del,
c.5409>A, c.181T>G, c.3343del, c.4356del, c.5503C>T and c.1508del. The two most common
BRCA2m present in our population were c.6641dup (5 patients, 9%) and c.9371A>T (3
patients, 6%). Other BRCA2m detected in 2 patients were c.5073dup and c.8331+1G>T and
in 1 patient were c.6486_6489del, c.4593del, 3663delT, c.4563_4564del, c.6037A>T and
c.9286G>T.
CONCLUSION: The most common BRCA1m in our study (c.5266dup, p.Gln1756fs) is the
most common mutation among other Slavic countries such as Russia, Belarus, Poland, Czech
Republic, Slovenia as well as in northern Greece, the second common in the Ashkenazi Jewish
population, and the third common in North Africa (Marocco, Algeria and Tunis). |
