in Cancer
Somatic mutation
A change in the DNA sequence in
cells other than sperm or egg
The mutation is present in the
cancer cell and its offspring, but
not in the patient’s healthy cells
Germline mutation
A change in the DNA sequence that can be
inherited from either parent
Somatic mutation
A change in the DNA sequence in cells other than
sperm or egg
The mutation is present in the cancer cell and its
offspring, but not in the patient’s healthy cells
Mutations & cancer genes
• Cancer genes are causally implicated in oncogenesis
• Mutations in cancer genes can occur somatically or
can be inherited.
• Mutations in some cancer genes can be inherited
from parents, in which case they are present in
every cell of the body. Such people are at a higher
risk of developing cancer.
• Somatic mutations can occur in any of the cells of
the body except the germ cells (sperm and egg) and
therefore are not passed on to children.
• Cancer genes are causally implicated in oncogenesis
• Mutations in cancer genes can occur somatically or
can be inherited.
• Mutations in some cancer genes can be inherited
from parents, in which case they are present in
every cell of the body. Such people are at a higher
risk of developing cancer.
• Somatic mutations can occur in any of the cells of
the body except the germ cells (sperm and egg) and
therefore are not passed on to children.
Importance of somatic DNA
changes in human cancer
This piece of DNA is an exact copy of the DNA from which it came. When
the parent cell divided to create two cells, the cell's DNA also divided,
creating two identical copies of the original DNA.
1. DNA of a normal cell
Potongan DNA ini adalah salinan persis DNA dari mana asalnya. Ketika sel
induk dibagi untuk membuat dua sel, DNA sel juga dibagi, menciptakan
dua salinan identik dari DNA asli.
2. Mutation of DNA
Here is the same section of DNA but from another cell. If you can imagine that DNA
is a twisted ladder, then each rung of the ladder is a pair of joined molecules, or a
base pair. With this section of DNA, one of the base pairs is different from the
original.
This DNA has suffered a mutation, either through mis-copying (when its parent cell
divided), or through the damaging effects of exposure to radiation or a chemical
carcinogen.
2. Mutation of DNA
Ini bagian DNA yang sama tetapi dari sel lain. Jika Anda dapat membayangkan bahwa
DNA adalah tangga bengkok, maka setiap anak tangga adalah sepasang molekul yang
bergabung, atau pasangan basa. Dengan bagian DNA ini, salah satu pasangan basa
berbeda dari aslinya. DNA ini telah mengalami mutasi, baik melalui penyalinan yang
salah (ketika sel induknya terbelah), atau melalui efek merusak dari paparan radiasi
atau karsinogen kimia.
3. Genetically altered cell
Body cells replicate through mitosis, they respond to their surrounding cells and
replicate only to replace other cells. Sometimes a genetic mutation will cause a
cell and its descendants to reproduce even though replacement cells are not
needed.
The DNA of the cell highlighted above has a mutation that causes the cell to
replicate even though this tissue doesn't need replacement cells at this time or at
this place.
3. Genetically altered cell
The genetically altered cells have, over time, reproduced unchecked, crowding out
the surrounding normal cells. The growth may contain one million cells and be the
size of a pinhead. At this point the cells continue to look the same as the
surrounding healthy cells.
After about a million divisions, there's a good chance that one of the new cells
will have mutated further. This cell, now carrying two mutant genes, could have
an altered appearance and be even more prone to reproduce unchecked.
4. Spread and second mutation
Sel-sel yang diubah secara genetik, dari waktu ke waktu, telah bereproduksi tanpa
diperiksa, memadati sel-sel normal di sekitarnya. Pertumbuhannya mungkin
mengandung satu juta sel dan seukuran kepala pin. Pada titik ini sel-sel terus
terlihat sama dengan sel-sel sehat di sekitarnya. Setelah sekitar satu juta divisi, ada
peluang bagus bahwa salah satu sel baru akan bermutasi lebih lanjut. Sel ini,
sekarang membawa dua gen mutan, bisa memiliki penampilan yang berubah dan
bahkan lebih rentan untuk bereproduksi.
5. Third mutation
Not all mutations that lead to cancerous cells result in the cells reproducing at a
faster, more uncontrolled rate. For example, a mutation may simply cause a cell to
keep from self-destructing. All normal cells have surveillance mechanisms that look
for damage or for problems with their own control systems. If such problems are
found, the cell destroys itself.
Over time and after many cell divisions, a third mutation may arise. If the mutation
gives the cell some further advantage, that cell will grow more vigorously than its
predecessors and thus speed up the growth of the tumour.
5. Third mutation
Tidak semua mutasi yang mengarah ke sel kanker menghasilkan sel bereproduksi
pada tingkat yang lebih cepat dan lebih tidak terkontrol. Sebagai contoh, mutasi
dapat menyebabkan sel agar tidak merusak diri sendiri. Semua sel normal memiliki
mekanisme pengawasan yang mencari kerusakan atau masalah dengan sistem
kontrol mereka sendiri. Jika masalah seperti itu ditemukan, sel itu menghancurkan
dirinya sendiri. Seiring waktu dan setelah banyak pembelahan sel, mutasi ketiga
mungkin muncul. Jika mutasi memberi sel keuntungan lebih lanjut, sel itu akan
tumbuh lebih kuat dari pendahulunya dan dengan demikian mempercepat
pertumbuhan tumor.
6. Fourth mutation
The new type of cells grow rapidly, allowing for more opportunities for
mutations. The next mutation paves the way for the development of an even
more aggressive cancer.
Jenis sel baru tumbuh dengan cepat, memungkinkan lebih banyak peluang untuk
mutasi. Mutasi berikutnya membuka jalan bagi perkembangan kanker yang bahkan
lebih agresif. Pada titik ini tumor masih terkandung.
7. Breaking through the
membrane
The newer, wilder cells created by another mutation are able to push their way
through the epithelial tissue's basement membrane, which is a meshwork of protein
that normally creates a barrier. The invasive cells in this tumour are no longer
contained.
Sel-sel yang lebih baru, lebih liar yang diciptakan oleh mutasi lain mampu mendorong
jalan mereka melalui membran basement jaringan epitel, yang merupakan kerja
protein yang biasanya menciptakan penghalang. Sel-sel invasif dalam tumor ini tidak
lagi terkandung. Pada titik ini kankernya masih terlalu kecil untuk dideteksi.
8. Angiogenesis
Often during the development of earlier stages of the tumour, or perhaps by the
time the tumour has broken through the basement membrane (as pictured above),
angiogenesis takes place. Angiogenesis is the recruitment of blood vessels from the
network of neighbouring vessels.
Without blood and the nutrients it carries, a tumour would be unable to continue
growing. With the new blood supply, however, the growth of the tumour
accelerates; it soon contains thousand million cells and, now the size of a small
grape, is large enough to be detected as a lump
8. Angiogenesis
Seringkali selama perkembangan tahap-tahap awal tumor, atau mungkin pada saat
tumor telah menembus membran dasar (seperti yang digambarkan di atas),
angiogenesis terjadi. Angiogenesis adalah perekrutan pembuluh darah dari jaringan
pembuluh yang berdekatan.
Tanpa darah dan nutrisi yang dibawanya, tumor tidak akan dapat terus tumbuh.
Namun, dengan suplai darah baru, pertumbuhan tumor bertambah cepat; segera
mengandung ribuan juta sel dan, sekarang ukuran anggur kecil, cukup besar untuk
dideteksi sebagai benjolan
9.Invasion and dispersal
The tumour has now invaded the tissue beyond the basement membrane.
Individual cells from the tumour enter into the network of newly formed
blood vessels, using these vessels as highways by which they can move to
other parts of the body. A tumour as small as a gram can send out a million
tumour cells into blood vessels a day.
9.Invasion and dispersal
Metastasis is now
underway, as tumour cells
from the original cancer
growth travel throughout
the body. Most of these
cells will die soon after
entering the blood or lymph
circulation.
Apa yang membuat sebagian
10. Tumour cells besar tumor sangat
mematikan adalah
travel - metastasis kemampuan mereka untuk
bermetastasis - yaitu,
membangun situs tumor
baru di lokasi lain di seluruh
tubuh. Tumor sekunder.
Metastasis sekarang sedang
berlangsung, ketika sel-sel
tumor dari pertumbuhan
kanker asli menyebar ke
seluruh tubuh. Sebagian
besar sel-sel ini akan mati
segera setelah memasuki
sirkulasi darah atau getah
bening.
11. Metastasis
To form a secondary tumour, a tumour cell needs to leave the vessel system and
invade tissue. The cell must attach itself to a vessel's wall. Once this is done, it can
work its way through the vessel and enter the tissue.
Although perhaps less than one in 10,000 tumour cells will survive long enough to
establish a new tumour site, a few survivors can escape and initiate new colonies
of the cancer.
11. Metastasis