It now seems fundamentally difficult to accept the concept of a cancer without genetic mutation. Assuming a case of genetic mutation without cancer would be published, one can certainly assume that a mutation exists but has not been detected.

Best regards

I believe there are no cancers without mutations...

Might be glioma with MGMT methylation.

Thank you very much Michel and Vladimir for your responses that I shared at 100% (and even more if it would be possible!!).

So, what do you think about some theories recently emphasized about the fact that some cancer types initially occur without genomic mutations.

I will thus reformulate my initial question in: "WHAT IS THE MOST ADVANCED STAGE AND THE HISTOLOGICAL TYPE OF AN ACTUAL MALIGNANT TISSUE (i.e. A CANCER) IN WHICH NO GENOMIC MUTATION HAS BEEN EVIDENCED?

Dear Krishnanand: gliomas are characterized by an amazing "constellation" of genomic mutations, which will even lead to new malignancy grading schemes of gliomas.

Best regards

Robert

Chronic inflammation or the inflammatory microenvironment can lead to cancer by different ways.

Elevated level of certain cytokines e.g. IL-1b and its polymorphism (in Helicobacter pylori infection) can be associated with the expansion of myeloid-derived supressor cells and the development of gastric cancer. (DOI 10.1016/j.ccr.2008.10.011)

Changes in miRNA expression under inflammatory circumstances can support tumorigenesis since e.g. mir155 inhibits mismatch repair, (www.pnas.org/cgi/doi/10.1073/pnas.1101795108)

Reduced circulation (e.g. in testis, varicocele) causes hypoxia, hypoxia is not only the consequence but also can be a cause of cancer development since stabilized HIF1a can mediate epithelial-mesenchymal transition (proliferation, survival)(DOI:10.1371/journal.pone.0129603)

There are several other examples linking inflammation and cancer. In this relation genetic mutations can be caused by inflammatory mediators e.g. ROS, ROI, RNS also...Chronic inflammation can lead to genome instability (doi: 10.1093/carcin/bgp127).

Regarding your question, in my opinion it is possible to develop cancer under chronic inflammatory conditions without prior driver mutations but when cancer is established mutations will accumulate.

Yes Gabor, I perfectly understand your point of view.

Thus, I will now raise a sub-sub-question thanks to your comments: "ARE GENOMIC MUTATIONS CAUSES OR CONSEQUENCES OF THE MALIGNANT TRANSFORMATION OF A TISSUE"?

For sure, some of them are consequences ... but what about the remaining ones?

Best regards

Robert

I fully agree with your comments Reinert!

And we can even go further in these arguments: are genomic mutations occuring at random? If yes, some are lethal for life (at the cellular level first and then ...), some bring nothing as disadvantages or advantages in terms of life competition, while others will bring significant advantages in terms of evolution, first at the level of a cell, and then at the level of a "coordinated organism". Cancers could maybe simply reflect this fact, but in an anarchic way ???

Best regards

Robert

I strongly recommend to see the book recently publishrd in Acad.Press by Andrey Kozlov

Below see eference on hiss paper on the subject

Med Hypotheses. 2010 Jan;74(1):177-85. doi: 10.1016/j.mehy.2009.07.027. Epub 2009 Aug 8.

The possible evolutionary role of tumors in the origin of new cell types.

Kozlov AP1.

Thank you Vladimir. I will try to get this book.

Yes, indeed Reinert!

Robert

May be with minimal acquisition of hits (mutations) involving the genome

For example, MLL Rearranged ALL (Infant ALL)

It was demonstrated that this type of leukemia was initiated by MLL rearrangement as the 1st hit with close to 100% concordance rate in monozygotic twins.

There is an open debate about the presence of the 2nd hit (mutation).

Heat Map for Copy Number Alteration (CNA) revealed a silent genomic landscape.

It is proposed that the 2nd hit may be acquired at the level of the Epigenetics

Thank you very much Ahmed!

Robert

There may be a hidden question here regarding whether  evolution of human happened through mutation? because, basically  tumor is a growth of new organ.

Sincerely

Not at all Krishnanand!

An organ is by definition an organized network of tissues, which in turn are organized networks of cell populations, and this organ fit in with one or several physiological functions.

A cancer is an anarchic mass composed of multiple cell populations that do not fit in with physiological functions, but that destroy normal organs.

I sincerely hope for you that your genome will mimic a cancer tissue the latest possible if you want to stay a long time on Earth ...

Best regards

Robert

Dear Sir

here is one example, the growth of tumor doesn't mean the growth of complete new organ.Because during organogenesis every organ is just a ball of mass. Growth of tumor or indirectly organ growth with function can be seen in gigantism.

Gigantism is a serious condition that is nearly always caused by an adenoma, a tumor of the pituitary gland.  The pituitary tumor cells secrete too much growth hormone (GH), leading to many changes in the body.

sincerely

Dear Krishnanand ...

We are speaking about cancers ... i.e. malignant tumors, not about benign tumors, which are not at all cancers ...

Les than 5% of benign tumors will give cancers (and this is usally heredity or virus infection).

Gigantism has nothing to do with cancers ...

The "ball of mass" you are referring to during organogenesis faces extraordinary programs of differentiation ... leading them to organs ...

I would be more than interested if you could provide me with such (top-articles) about cancers ...

And please, do not come back with teratoma as an example because I have to admit that I have not too much time to provide basic courses of tumor biology.

Best regards

Robert

Kansere Son