Gambaran Genetik Pada Mola Hidatidosa dan Koriokarsinoma (Studi Pustaka).

ABSTRAK

GAMBARAN GENETIK PADA MOLA HIDATIDOSA DAN
KORIOKARSINOMA
Inga Mulyani Dewi Santoso, 2007
Andries,

Pembimbing Utama : Freddy Tumewu
dr., MS

Mola hidatidosa dan koriokarsinoma merupakan jenis Penyakit Trofoblastik
Gestasional (PTG) yang paling sering terjadi pada wanita hamil. Insidensinya
meningkat dengan mortalitas yang tinggi terutama pada masyarakat Asia.
Pengetahuan mengenai etiologi dan faktor risiko dianggap tidak cukup
menjelaskan pada sebagian kasus yang terjadi. Adapun peningkatan mortalitas ini
dipengaruhi oleh transformasi mola menjadi koriokarsinoma. Sehingga faktor
pemicu mola merupakan pemicu pula untuk koriokarsinoma, yaitu pengaruh gizi,
riwayat kehamilan, etnik, golongan darah, dan genetik.
Faktor genetik yang terbukti berperan pada mola hidatidosa antara lain gen
H19, gen CDKN1C, gen ZNF127, gen p16, HIC-1, TIMP3, GSTP1, DAPK, Ecadherin, gen NALP7, gen dalam kromosom 19q13.4, gen ZO-1 dan Occludin,
sedangkan pada koriokarsinoma antara lain gen H19 & IGF-2, Maspin, NECC1,

JAR & JER-3, gen c-ras, c-erbB-2, p53 dan nm23, gen HOX, faktor Mash-2, cmyc dan ras RNA, gen Bcl-2 dan Bax, gen EGFR, c-erbB-3, Onkogen c-erbB-4,
gen DOC-2/hDab2, gen Cyclin E, gen P2Y6. Faktor genetik ini terbukti
diturunkan secara autosom resesif. Kemampuan pengetahuan di bidang genetika
diharapkan mampu memberi banyak informasi.
Kesimpulannya, genetik mempunyai peran dalam terjadinya mola hidatidosa
dan koriokarsinama.
Kata kunci : mola hidatidosa, koriokarsinoma, ekspresi gen pada mola hidatidosa,
ekspresi gen pada koriokarsinoma.

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ABSTRACT

GENE EXPRESSION ON MOLA HYDATIFORM AND
CHORIOCARCINOMA

Inga Mulyani Dewi Santoso, 2007

Tutor: Freddy Tumewu Andries, dr., MS

Hydatidiform mole and choriocarcinoma are the forms of Gestational
Trophoblastic Neoplasia (GTN), which commonly develop in pregnant woman.
The incident has increased with the highest mortality occur in Asia. Etiology and
risk factors are inadequately considered to explain some of the cases. There is
also an increased mortality associated with the transformation of mole into
choriocarcinoma. Therefore, risk factors for hydatidiform mole will also be the
risk factors for choriocarcinoma, which include malnutrition, pregnancy history,
ethic, blood type, and genetics.
The genes contribute in hydatidiform mole are H19, CDKN1C, ZNF127, p16,
HIC-1, TIMP3, GSTP1, DAPK, E-cadherin, NALP7, gene in chromosom 19q13.4,
ZO-1 and Occludin; whereas in choriocarcinoma are H19 and IGF2, Maspin,
NECC1, and JAR and JER3, gene c-ras, c-erbB-2, p53 and nm23, HOX, factor
Mash-2, c-myc and ras RNA, Bcl-2 and Bax, EGFR, c-erbB-3, Onkogen c-erbB4, DOC-2/hDab2, Cyclin E, P2Y6. These genes are inherited as autosomal
recessive traits. The finding of greater ability to gain more knowledge on genetics
is expected to give plenty more information.
In conclusion, hydatidiform mole and choriocarcinoma are diseases that
implicate genetic factors as the primary cause.
Keyword: mola hydatiform, choriocarcinoma, gene expression on mola
hydatiform, gene expression on choriocarcinoma.

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Halaman
JUDUL ......................................................................................................................... i
LEMBAR PERSETUJUAN ........................................................................................ ii
SURAT PERNYATAAN ........................................................................................... iii
ABSTRAK ................................................................................................................. iv
ABSTRACT.................................................................................................................... v
KATA PENGANTAR ............................................................................................... vi
DAFTAR ISI............................................................................................................. viii
DAFTAR GAMBAR ................................................................................................. xi

BAB I PENDAHULUAN ........................................................................................... 1
1.1 Latar belakang ...................................................................................................... 1
1.2 Identifikasi Masalah ............................................................................................. 2
1.3 Maksud dan Tujuan .............................................................................................. 2

1.4 Metode Penulisan ................................................................................................. 2

BAB II TINJAUAN PUSTAKA ................................................................................ 3
2.1 Sistem Reproduksi Wanita .................................................................................... 3
2.1.1 Anatomi, Histologi, dan Fisiologi .......................................................... 3
2.1.1.1 Vagina ........................................................................................ 4
2.1.1.2 Uterus ......................................................................................... 5
2.1.1.3 Tuba Uteri Falopii ....................................................................... 7
2.1.1.4 Ovarium ..................................................................................... 8
2.1.2 Kehamilan Normal.... ........................................................................... 10
2.1.2.1 Pelepasan dan Transport Gamet ............................................... 10
2.1.2.2 Fertilisasi .................................................................................. 10
2.1.2.3 Implantasi.................................................................................. 10
2.1.2.4 Perubahan yang Terjadi Selama Kehamilan .............................. 12

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2.2 Gambaran Umum Penyakit Trofoblastik Gestasional ........................................ 13
2.2.1 Definisi Penyakit Trofoblastik Gestasional ......................................... 13
2.2.2 Prevalensi Penyakit Trofoblastik Gestasional ...................................... 15
2.2.3 Klasifikasi Penyakit Trofoblastik Gestasional ..................................... 16
2.2.3.1 Mola Hidatidosa ....................................................................... 16
2.2.3.1.1 Mola Hidatidosa Komplit (MHK) .................................. 20
2.2.3.1.2 Mola Hidatidosa Partial (MHP) ...................................... 22
2.2.3.1.3 Persistent Trophoblastic Tumor (PTT) ........................... 24
2.2.3.2 Tumor Trofoblas Gestasional (TTG) ....................................... 25
2.2.3.2.1 Koriokarsinoma ............................................................... 26
2.2.3.2.2 Mola Invasif (MI) ........................................................... 30
2.2.3.2.3 Placental Site Trophoblastic Tumor (PSTT) .................. 31
2.2.4 Stadium Penyakit Trofoblastik Gestasional .......................................... 33
2.3 Sitogenetika Pada Mola Hidatidosa dan Koriokarsinoma .................................. 36
2.3.1 Mola Hidatidosa Komplit .................................................................... 36
2.3.2 Mola Hidatidosa Partial ....................................................................... 39
2.3.3 Koriokarsinoma .................................................................................... 40
2.4 Pemetaan Genom Pada Mola Hidatidosa dan Koriokarsinoma .......................... 41
2.4.1 Mola Hidatidosa ................................................................................... 41
2.4.1.1 Gen H19 ................................................................................... 41

2.4.1.2 Gen CDKN1C .......................................................................... 41
2.4.1.3 Gen ZNF127 ............................................................................. 42
2.4.1.4 Gen p16, HIC-1, TIMP3, GSTP1, DAPK, E-cadherin ............ 42
2.4.1.5 Gen NALP7 .............................................................................. 42
2.4.1.6 Gen dalam Kromosom 19q13.4 ............................................... 42
2.4.1.7 Gen ZO-1 dan Occludin ........................................................... 43
2.4.2 Koriokarsinoma .................................................................................... 43
2.4.2.1 Gen H19 dan IGF-2 ................................................................. 43
2.4.2.2 Gen Maspin .............................................................................. 44
2.4.2.3 Gen NECC1 ............................................................................. 44
2.4.2.4 Gen JAR dan JER-3 ................................................................. 44

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2.4.2.5 Gen c-ras, c-erbB-2, p53, dan nm23 ........................................ 45
2.4.2.6 Gen HOX .................................................................................. 45
2.4.2.7 Faktor Mash-2, c-myc dan ras RNA ........................................ 45
2.4.2.8 Gen Bcl-2 dan Bax .................................................................... 46

2.4.2.9 Gen EFGR, c-erbB-3, onkogen c-erbB-4 ................................. 46
2.4.2.10 Gen DOC-2/hDab-2 ............................................................... 47
2.4.2.11 Gen Cyclin E .......................................................................... 47
2.4.2.12 Gen P2Y6 ............................................................................... 47
BAB III PEMBAHASAN ......................................................................................... 48
BAB IV KESIMPULAN DAN SARAN .................................................................. 55
4.1 Kesimpulan ......................................................................................................... 55
4.2 Saran ................................................................................................................... 55
DAFTAR PUSTAKA ............................................................................................... 56
RIWAYAT HIDUP PENULIS ................................................................................. 61

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DAFTAR GAMBAR

Halaman

Gambar 2.1 Sistem Reproduksi Wanita ...................................................................... 3
Gambar 2.2 Ovarium .................................................................................................. 8
Gambar 2.3 Histologi Siklus Ovarium ........................................................................ 9

Gambar 2.4 Perkembangan Zygot dan Proses Implantasi ........................................ 11
Gambar 2.5 Gelembung Mola.................................................................................... 17
Gambar 2.6 Histopatologi Koriokarsinoma .............................................................. 26
Gambar 2.7 Histopatologi Mola Invasif ................................................................... 30
Gambar 2.8 Histopatologi Placental Site Trophoblastic Tumor .............................. 31
Gambar 2.9 Diploid Androgenetik ........................................................................... 38
Gambar 2.10 Diandro Triploid ................................................................................. 40

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BAB I
PENDAHULUAN

1.1 Latar belakang

Pada umumnya pada setiap kehamilan akan berakhir dengan lahirnya bayi
yang cukup bulan, sehat dan sempurna. Akan tetapi, ada kalanya terdapat
gangguan perkembangan yang dapat menyebabkan kegagalan dalam kehamilan.
Salah satu bentuk dari kegagalan kehamilan adalah hasil dari konsepsi yang tidak

berupa janin, melainkan berkembang patologis berupa gelembung seperti anggur
yang dikenal sebagai hamil anggur / mola hidatidosa yang mana kehamilan ini
dapat mengalami tranformasi keganasan menjadi Tumor Trofoblas Gestasional
(TTG) (Djamhoer, 2005).
Mola dan tumor trofoblastik merupakan jenis dari Penyakit Trofoblastik
Gestasional (PTG) yang paling sering terjadi dan berprognosa buruk, bagi janin
maupun ibu. Jenis lainnya adalah mola invasif dan Placenta Site Trophoblastic
Tumor (PSTT) yang merupakan transformasi lanjut dari mola maupun
koriokarsinoma (Evans, Soper, Hammond, 2003). Sampai saat ini belum diketahui
dengan jelas mengapa dan bagaimana sel trofoblas yang tadinya normal, suatu
waktu dapat berubah menjadi ganas. Dengan kata lain, teori karsinogenesis pada
TTG masih kabur begitu juga dengan aplikasi klinisnya. Yang telah disepakati
mengenai transformasi ini adalah adanya ketidakseimbangan antara onkogen dan
tumor supresor gen, dimana jumlah onkogen menjadi lebih dominan. Akan tetapi,
belum dapat dipastikan onkogen atau tumor supresor gen yang mana yang paling
berperan, apakah gen Bcl-2 EGF, H19, p15, p53, c-erbB-2, c-myc atau yang
lainnya (Djamhoer, 2005). Oleh karena itu, penelitian di bidang genetik masih
terus dilakukan pada mola dan tumor trofoblastik dengan tujuan agar kelainan ini
dapat dideteksi secara lebih dini (Surti, 2005).
Di Indonesia, penyakit trofoblastik gestasional ini masih merupakan masalah

pelayanan kesehatan reproduksi yang besar karena prevalensi yang tinggi, faktor
risiko yang banyak, penyebaran yang merata. Ternyata hal ini bukan semata-mata

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karena faktor sosioekonomi dan budaya saja (Djamhoer, 2005). Akan tetapi
dengan adanya suatu perubahan pada struktur genetika juga merupakan salah satu
penyebab dari penyakit trofoblastik gestasional.
Saat konsepsi, dimana sel telur akan dibuahi oleh sperma, bila keduanya
normal, maka kehamilan penyakit trofoblastik gestasional ini dapat terhindarkan.
Akan tetapi, bila salah satu dari sel telur ataupun sperma mengalami pembelahan
yang tidak sempurna maka risiko penyakit trofoblastik gestasional akan
meningkat. Oleh karena itu, dengan memahami risiko genetik, sebagai salah satu
penyebabnya akan sangat membantu dalam menegakkan diagnosa dan pengobatan
terhadap penyakit trofoblastik gestasional terutama mola hidatidosa dan
koriokarsinoma secara lebih dini (Djamhoer, 2005).

1.2. Identifikasi Masalah

Gen apakah yang menjadi faktor risiko timbulnya mola hidatidosa dan
koriokarsinoma.

1.3. Maksud dan Tujuan

Maksud : Untuk mempelajari lebih lanjut gambaran genetik pada mola
hidatidosa dan koriokarsinoma.
Tujuan : Mengumpulkan informasi dari studi-studi terkini mengenai gen-gen
yang turut berperan dalam mola hidatidosa dan koriokarsinoma.

1.4. Metode Penulisan

Metode yang dipergunakan dalam penulisan Karya Tulis Ilmiah ini adalah
Studi Pustaka.

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BAB IV
KESIMPULAN DAN SARAN

4.1 Kesimpulan

Gen-gen yang berperan dalam timbulnya mola hidatidosa baik komplit
maupun parsial antara lain lain gen H19, gen CDKN1C, gen ZNF127, gen p16,
HIC-1, TIMP3, GSTP1, DAPK, E-cadherin, gen NALP7, gen dalam kromosom
19q13.4, gen ZO-1 dan Occludin.
Gen-gen yang berperan dalam kejadian koriokarsinoma antara lain gen H19 &
IGF-2, Maspin, NECC1, JAR & JER-3, gen c-ras, c-erbB-2, p53 dan nm23, gen
HOX, faktor Mash-2, c-myc dan ras RNA, gen Bcl-2 dan Bax, gen EGFR, c-erbB3, Onkogen c-erbB-4, gen DOC-2/hDab2, gen Cyclin E, gen P2Y6.
Sedangkan gen yang dapat menimbulkan kejadian baik mola hidatidosa
maupun koriokarsinoma diantaranya adalah gen DOC-2/hDab2, gen ZO-1 dan
Occludin, gen c-ras, c-erbB-2, p53 dan nm2, gen EGFR, c-erbB-3, Onkogen cerbB-4, gen p16, HIC-1, TIMP3, GSTP1, DAPK, E-cadherin.

4.2 Saran

Dengan mengetahui faktor pemicu selain genetik, diharapkan wanita yang
hamil sadar untuk menghindari faktor pemicu tersebut, sehingga prevalensi
timbulnya kelainan pada perkembangan kehamilan dan plasenta dapat ditekan.
Perlu ditingkatkan pemeriksaan secara sitogenetika pada koriokarsinoma yang
memiliki prognosis paling jelek diantara Penyakit Trofoblastik Gestasional
(PTG).
Karena setiap penyakit yang terdeteksi lebih dini akan menghasilkan
prognosis yang lebih baik, maka diperlukan teknik-teknik untuk mengidentifikasi
gen-gen yang terlibat secara lebih cepat dan akurat. Teknik-teknik tersebut juga
hendaknya dipublikasikan pada masyarakat.

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