Genomic hybridization and analysis

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11/28/2010 10:23am
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Replies: 13

Is doing genomic hybridization and analysis "standard" practice these days for melanoma patients?

If so, are there locations that are more skilled at performing the tests? From my understanding, Boris Bastian is a pioneer in this field, but because of his recent move from UCSF to Sloan Kettering, his lab is not yet prepared to do the testing. He suggested that we seek advice from his prior colleagues at UCSF.

Josiah's pathology report specifically suggests that we seek testing from Sloan Kettering, but when I questioned our Oncologist, he said the testing was already being done "in-house" at Dana-Farber. But why then would the pathologist suggest we go elsewhere for the testing?? I need to pursue that particular question to get answers.

I'd say no, it's not 'standard practice' I've had melanoma since 1983 and I've never been tested. I've had two progressions in this century and it's never even been suggested.

As to your pathologist recommendation, perhaps he did not know that Dana Farber is now doing testing, and just gave you the best info he could. Pretty impressive to me, actually, that he suggested it at all.

good luck!

dian

Dear Melanoma Mom,

Did your doctors explain how this testing would be used to guide their treatment of your Josiah? I was just researching it and there doesn't seem to be any specific treatments associated with the results generated by this form of tumor analysis...unless I am missing something. 

Interestingly...there are two terms that come up when researching "genomic hybridization" online...these are:
1) Chromosomal Microarray Analysis (CMA) is a molecular-cytogenetic method for the analysis of copy number changes (gains/losses) in the DNA content of a given subject's DNA and often in tumor cells.
2) Comparative genomic hybridization (CGH) which will detect only unbalanced chromosomal changes. Structural chromosome aberrations such as balanced reciprocal translocations or inversions cannot be detected, as they do not change the copy number.  

Upon performing a search on this bulletin...your posting is the first (and only) one to mention any of these terms. 

If anyone has any knowledge of these methodologies please share with us.

I am hoping and praying for the best for Josiah. It pains me greatly to think that he is having to deal with all of this at his age. 

Best regards,
Mark from California

From what I understand, Boris Bastian was researching it as a tool to detect benign nevi, particularly in young patients and "unusual' cases, and melanoma. It is too bad he moved from UCSF, he was the one who tested Bens tumor for Ckit at my request.

Anyway...keep researching!

Becky

Without going into the fine detail - because there is lots of it - Josiah's case is very, very unusual. I have brought up the question as to whether this could possibly be benign nevi which is sometimes close to impossible to tell the difference from melanoma, but the Oncologist and surgeon shot me down. But the pathology report is definitely leaving that door open just a bit, if you ask me, and I think that is why he suggests having the testing done to be 100% sure what we are dealing with. 

So, am I to understand that testing for BRAF, c-kit and other mutations is a whole separate deal? 

I think it is different than the genetic testing, but Bens tumor was tested for Ckit, Braf and a couple of others all at the same time.

Ben's case was very unusual too...tip of tongue, his age...and it was sent to 3 pathologists, the first two said melanoma, the third said something a little more ambiguous...and of course I was grasping at any possibilities that it was not melanoma. But since it has spread to one lymph node (although 3rd pathologist said in report that, rarely, non-melanoma nevi can metastisize) they went under the assumption that it is melanoma and treated as such. The genetic testing was not brought up to us.

I know that they were expecting to find metastasis b/c they had Josiah do all the scans before the SNB. And that the SNB was clear, after having a 14mm lesion, is miraculous in my book.

So I guess that is why I continue to struggle with the ambiguous wording in the report and his specific suggestion to send the slides to a certain physician who would do the hybridization. Did he have doubt?? If there is even a 5% doubt in his mind, I feel we should pursue further testing. No one else (our oncologists, my husband) seems to think this is worthy of the great amount of thought I have put into this thus far. Call it mother's intuition, or craziness, but I feel we need to take this next step, even if it only confirms the melanoma diagnosis.

Given that the lesion did not present with any of the Typical characteristics of melanoma, I could see why the doctor would want to confirm the diagnosis before putting Josiah through any further treatments for melanoma. This further (unusual) step does seem to make sense...particularly if it would provide the doctor with enough definitive evidence to dictate a different course of treatment...and perhaps no futher active treatment for Josiah from the sounds of it.

Good luck in this promising pursuit! Keep us posted.

Regards,
Mark from California

I think the lesion presented *some* characteristics of melanoma and *some* that were not. That is what they told me from the punch biopsy initially and they took weeks to finally classify it as "most likely" melanoma. But they weren't willing to be certain until the lesion was removed. While the surgeon and oncologist state to me that the pathologists "are sure" that it is melanoma, there is language in the reports that lead me to think that there might have been a bit of doubt. 

For example,

"Many of the cells have spitzoid characteristics."

"Mitoses are relatively uncommon and the mitotic rate is 2/mm2."

"Although the lesion demonstrates a constellation of findings consistent with a malignant neoplasm, the lesion nonetheless exhibits some spitzoid phenotypic characteristics. I believe it is reasonable to designate this lesion as melanoma with some spitzoid characteristics. An alternative designation might be malignant spitzoid melanocytic tumor or neoplasm."

"Given the striking epithelioid (Sptiz-like) cytomorphology, the tumor may not have equivalent biologic potential compared with nodular (non-epitheloid) melanoma in adults."

So .... what is that last quote supposed to tell us???

I'm probably barking up the wrong tree and you are all welcome to *kindly* tell me that. 

Dr. Boris Bastian's profile on Sloan-Kettering's website explains the latest direction of his research efforts and really clarifies the goals he has for his efforts...

http://www.mskcc.org/mskcc/html/98271.cfm

Our laboratory's research interest is focused on the molecular genetics of melanoma with a particular focus on the discovery on genetic alterations useful for diagnosis, classification, and therapy. Using genome-wide DNA copy and mutation analyses and by correlating them with clinical and histomorphologic features we have identified distinct subtypes of melanoma. These findings have become clinically relevant, as the subtypes are enriched in specific mutations such as in KIT and BRAF, for which specific inhibitors are already approved or under advanced clinical investigation. We believe that an improved disease classification with the precise delineation of biologically distinct, molecularly defined subtypes is the key to improving prevention, diagnosis, and therapy of melanoma.

More recently, we have identified mutations in the heterotrimeric G-protein GNAQ in uveal melanoma and in melanocytic tumors that arise in the dermis. Our current research interest is focused on understanding the signaling downstream of these mutations to identify targets for therapeutic intervention. We are pursuing a multi-pronged approach using genomics, proteomics, high-throughput RNAi and drug screens and are developing preclinical models to help accelerate the clinical translation of these findings.

In addition, we are developing molecular assays to assist in the distinction of malignant and benign melanocytic tumors. We have found that comparative genomic hybridization and fluorescence in situ hybridization can assist in classifying tumors that have equivocal histopathologic features and cannot be reliably diagnosed as benign or malignant with current methods.

Based on the last paragraph of Dr. Bastian's profile, I think you are right to pursue this avenue to its full potential. Why put Josiah through treatment for melanoma just because of the limitations of current diagnostic methods.

It sounds like you doctor is already investigating the possibility of mis-diagnosis...though they might not be telling you too much right now because they may not want you to get your hopes up too high until they know more.

I agree. Is the "in house" testing at Dana Farber the same as what Dr Bastian is researching? Maybe you should contact the melanoma specialists at UCSF and explain the situation and that Dr Bastian referred you to them.

I also found this long but interesting article you should take a look at

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797485/?tool=pubmed

Once again, thank you to everyone for your help and encouragement. I am going to use the next two weeks (while things are relatively quiet - no trips to Boston! Yay!) to do tons of research and make some calls. My gut is telling me to pursue this, even if it only gives better clarification to Josiah's diagnosis and does not change matters.

Today I am meeting with a physician who approaches cancer treatment through non-traditional methods. I don't plan to turn Josiah into a raw food vegan or anything, but I figured that I would look into other methods to boost the immune system as well .... possibly juicing, supplements, acupuncture, etc. 

Becky, is your son on facebook? I thought it might be nice if our boys were in touch, in case Josiah wants to ask him any questions? If so, please send me info at jandehenderson@aol.com