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Scott Woodman, MD, PhD
ScottWoodmanMDPhD (Physician - Oncology - Hematology/Oncology (Verified) )| Communities: Melanoma (Cutaneous) | Answers: 8 |
| Member Since: Jul. 2012 |
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Professional Statement
Dr. Woodman is an assistant professor in the Departments of Melanoma Medical Oncology and Systems Biology at the University of Texas MD Anderson Cancer Center. He earned his M.D. and Ph.D (Molecular Pharmacology) through the NIH Medical Scientist Training Program at the Albert Einstein College of Medicine. He went on to the Beth Israel Deaconess Medical Center/Harvard Medical School for his internal medicine internship and residency training, and completed his medical oncology fellowship at the MD Anderson Cancer Center.
The primary focus of Dr. Woodman’s research laboratory is on understanding the molecular underpinnings of uveal (eye), mucosal and acral lentiginous melanomas, and on designing novel therapeutic approaches to these cancers. He is a principal investigator or co-investigator on multiple clinical trials. Dr. Woodman conducts a concerted, ongoing effort to translate his laboratory research findings into the clinic, and his clinical observations back to the laboratory.
Professional Info
Credential: MD
Primary specialty: Oncology - Hematology/Oncology
Medical school: Albert Einstein College of Medicine
Residency: Beth Israel Deaconess Medical Center/ Harvard Medical School
Internship: Beth Israel Deaconess Medical Center/ Harvard Medical School
Fellowship: MD Anderson Cancer Center/The University of Texas
Hospital affiliation: MD Anderson Cancer Center
Practice address:
7455 Fannin Street Unit Number: 904
Houston, TX
77054
Practice phone number: 713-792-0410
ScottWoodmanMDPhD Activities
A significant amount of research has gone into trying to elicit the clinical/pathological and/or chromosomal/molecular features of primary uveal melanomas that are predictive of developing metastatic disease. Clinical/pathological features that are associated with increased risk of metastatic disease include increased patient age, increased tumor diameter and thickness, involvement of the ciliary body, epithelioid cytology, extraocular extension, extravascular matrix patterns, and lymphocytic/monocytic infiltration into the tumor. However, no one of these features is as strongly predictive as particular chromosomal/molecular features.
Every normal cell has 22 pairs of chromosomes (i.e., two chromosome 1s, two chromosome 2s, etc.) and 2 sex chromosomes (XX = female or XY = male). In order to understand the nomenclature of chromosomal aberrations one must understand that each chromosome is structured such it contains a “short arm” referred to as ‘p’ and a “long arm” referred to as ‘q’ that emanate from a central point called the centromere. Primary uveal melanoma tumors tend to have very defined chromosomal alterations. Each tumor can have one of a number of chromosomal alterations: loss of p on chromosome 1, loss of an entire chromosome 3 (monosomy 3), gain of p on chromosome 6, loss of q on chromosome 6, loss of p on chromosome 8, and gain of q on chromosome 8. A tremendous amount of work has gone into trying to associate these chromosomal alterations with prognosis of metastatic disease. Among these chromosomal aberrations, the most powerful predictor of future metastatic disease is clearly the identification of monosomy 3 in a primary uveal melanoma tumor. The presence of 6p gain is nearly always mutually exclusive with monosomy 3 and predictive of not developing metastatic disease.
For the role of Gene Expression Analysis in predicting future metastatic disease seehttp://talkabouthealth.com/what-are-gene-expression-patterns-and-how-are-they-used-to-help-predict-prognosis-for-uveal-melanoma.
Currently, the most predictive, and thus employed factors, for assessing an individual patient’s risk of developing metastatic disease is monosomy 3 status (the presence of monosomy 3 being a poor prognostic factor) or gene expression profile (class 2 status being a poor prognostic factor).
Every normal cell has 22 pairs of chromosomes (i.e., two chromosome 1s, two chromosome 2s, etc.) and 2 sex chromosomes (XX = female or XY = male). In order to understand the nomenclature of chromosomal aberrations one must understand that each chromosome is structured such it contains a “short arm” referred to as ‘p’ and a “long arm” referred to as ‘q’ that emanate from a central point called the centromere. Primary uveal melanoma tumors tend to have very defined chromosomal alterations. Each tumor can have one of a number of chromosomal alterations: loss of p on chromosome 1, loss of an entire chromosome 3 (monosomy 3), gain of p on chromosome 6, loss of q on chromosome 6, loss of p on chromosome 8, and gain of q on chromosome 8. A tremendous amount of work has gone into trying to associate these chromosomal alterations with prognosis of metastatic disease. Among these chromosomal aberrations, the most powerful predictor of future metastatic disease is clearly the identification of monosomy 3 in a primary uveal melanoma tumor. The presence of 6p gain is nearly always mutually exclusive with monosomy 3 and predictive of not developing metastatic disease.
For the role of Gene Expression Analysis in predicting future metastatic disease seehttp://talkabouthealth.com/what-are-gene-expression-patterns-and-how-are-they-used-to-help-predict-prognosis-for-uveal-melanoma.
Currently, the most predictive, and thus employed factors, for assessing an individual patient’s risk of developing metastatic disease is monosomy 3 status (the presence of monosomy 3 being a poor prognostic factor) or gene expression profile (class 2 status being a poor prognostic factor).
New answer by ScottWoodmanMDPhD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
See the following answer -http://talkabouthealth.com/what-is-bap1-and-what-does-it-have-to-do-with-uveal-melanoma.
Normal cells have two copies of chromosome 3 (one from each parent). It has been known for quite some time that loss of one chromosome 3 (referred or as monosomy 3, because only one chromosome 3 remains) in a patient’s primary uveal melanoma tumor cells is highly predictive for the future development of metastatic uveal melanoma. Primary uveal melanoma tumors with cancer cells that are disomy (have both copies of chromosome 3) are highly associated with not developing metastatic uveal melanoma. A molecular reason for this disparity was unclear until the recent identification of mutations in BAP1 on the remaining chromosome 3 in the vast majority of uveal melanomas with monosomy 3, rendering the cells without functional BAP1.
Normal cells have two copies of chromosome 3 (one from each parent). It has been known for quite some time that loss of one chromosome 3 (referred or as monosomy 3, because only one chromosome 3 remains) in a patient’s primary uveal melanoma tumor cells is highly predictive for the future development of metastatic uveal melanoma. Primary uveal melanoma tumors with cancer cells that are disomy (have both copies of chromosome 3) are highly associated with not developing metastatic uveal melanoma. A molecular reason for this disparity was unclear until the recent identification of mutations in BAP1 on the remaining chromosome 3 in the vast majority of uveal melanomas with monosomy 3, rendering the cells without functional BAP1.
New answer by ScottWoodmanMDPhD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
BAP1 is a gene whose function is thought to suppress metastatic tumor formation/function in uveal melanoma. Every normal cell has two copies of chromosome 3 (one from each parent). A BAP1 gene is localized on each chromosome 3. Mutations in BAP1 result in the loss of its function as a tumor suppressor. Thus, when a uveal melanoma tumor is monosomy 3 (i.e., tumor cells contain only one chromosome 3) and have a mutation in the BAP1 gene on the remaining chromosome 3, BAP1 function is lost. This is technically referred to as a “loss of heterozygosity.” It was recently shown that approximately 85% of primary uveal melanomas that metastasize have BAP1 mutations.
Knowledge of the presence of a BAP1 mutation within a uveal melanoma tumor does not currently have an influence on treatment. However, research is beginning to reveal the molecular effects within a cell that result from the loss of BAP1, and there is a vested effort to develop therapeutic strategies to block these effects. There is also the potential to re-initiate the functions that BAP1 performs; however, restoring function versus blocking aberrant function of genes has been a more difficult therapeutic problem to solve.
Knowledge of the presence of a BAP1 mutation within a uveal melanoma tumor does not currently have an influence on treatment. However, research is beginning to reveal the molecular effects within a cell that result from the loss of BAP1, and there is a vested effort to develop therapeutic strategies to block these effects. There is also the potential to re-initiate the functions that BAP1 performs; however, restoring function versus blocking aberrant function of genes has been a more difficult therapeutic problem to solve.
New answer by ScottWoodmanMDPhD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
Each gene is a unique sequence of DNA (information) that is transcribed into messenger RNA (the “expression” of the information) which is translated into a particular protein (the ultimate functional unit in the cell for which the gene encoded). Not all of the approximately 23,000 genes in a cell are expressed (transcribed into messenger RNA), while some genes are expressed within tumor cells at higher or lower levels relative to normal cells. The level of expression for each gene within a tumor sample is referred to as the gene expression pattern. Multiple research groups have examined the gene expression pattern of primary uveal melanoma tumors and attempted to correlate specific patterns (sets of genes whose messenger RNA is elevated or decreased) with prognosis. Further refinement of this gene expression/prognosis correlation has demonstrated that the expression level of a small set of genes within a primary uveal melanoma tumor is very predictive of whether patients will ultimately manifest metastatic disease or not. These gene expression patterns have been termed class 1 (low risk of metastatic disease) and class 2 (high risk of metastatic disease).
New answer by ScottWoodmanMDPhD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
Approximately 85% of uveal melanoma tumors have somatic mutations (mutations in genes that are not inherited, but which occur sporadically) in the GNAQ or GNA11 genes. Mutations in the GNAQ or GNA11 genes are mutually exclusive, i.e., if a GNAQ mutation is present in a uveal melanoma tumor, then a GNA11 mutation is not present, and vice versa. Mutations in the GNAQ or GNA11 genes make the proteins they encode constantly overactive which drives the growth and survival of the uveal melanoma tumor cells. There is currently no drug that can directly inhibit the function of mutant GNAQ or GNA11, but there are clinical trials testing drugs in the attempt to block the “downstream” effects of mutant GNAQ or GNA11.
See this answer for the genetics concerning BAP1 -http://talkabouthealth.com/what-is-bap1-and-what-does-it-have-to-do-with-uveal-melanoma.
There are ongoing efforts to identify other genes apart from GNAQ/GNA11 or BAP1 that are mutated in uveal melanoma. Early results suggest that other gene mutations appear to be at much lower frequency and their functional significance will require further investigation.
Importantly, uveal melanomas, unlike other melanoma types, do not harbor a high frequency of mutations in the BRAF, NRAS or KIT genes. Thus, clinically available drug inhibitors for these genes (e.g., vemurafenib for BRAF or imatinib for KIT) are unlikely to play a role in uveal melanoma treatment.
See this answer for the genetics concerning BAP1 -http://talkabouthealth.com/what-is-bap1-and-what-does-it-have-to-do-with-uveal-melanoma.
There are ongoing efforts to identify other genes apart from GNAQ/GNA11 or BAP1 that are mutated in uveal melanoma. Early results suggest that other gene mutations appear to be at much lower frequency and their functional significance will require further investigation.
Importantly, uveal melanomas, unlike other melanoma types, do not harbor a high frequency of mutations in the BRAF, NRAS or KIT genes. Thus, clinically available drug inhibitors for these genes (e.g., vemurafenib for BRAF or imatinib for KIT) are unlikely to play a role in uveal melanoma treatment.
New answer by ScottWoodmanMDPhD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
There is not a universal standard for how patients that have no evidence of disease (NED) following treatment of their primary uveal melanoma should be followed. Typically, imaging is performed every 6 months to identify metastatic disease (uveal melanoma arising outside the eye). Either CT scans (preferably using a protocol that optimizes the contrast in the liver) or MRI scans are used. Abdominal ultrasound is also used, but does not always provide the best visualization of potential tumors within the liver. In addition to imaging studies, physicians tend to order some blood tests that measure liver function. There is an effort in the uveal melanoma clinical research community to adopt more universal standards, however studies to support clear recommendations are lacking. It is also the case that the genetics that underlie one’s uveal melanoma tumor may influence the type and time interval of follow-up screening (i.e., high risk vs. low risk of metastasis).
New answer by ScottWoodmanMDPhD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
Patients that have been treated for skin melanoma are at no greater risk of developing uveal melanoma as a result of treatments currently provided for skin melanoma. Although I assume that the underlying question being asked is whether people with skin melanoma are more at risk of developing uveal melanoma. Skin melanoma (with the exception of acral lentiginous skin melanoma) and uveal melanoma occur in higher frequency among people with fairer skin, light eye and hair color. In this sense, both forms of melanoma share a similar “at risk” population. However, there is little evidence that people who have had sporadic (not associated with inherited genetic aberrations) skin melanoma are at significantly higher risk of uveal melanoma.
There have been recent reports of families that harbor rare germline (inherited) mutations in BAP1 that make individuals within these families at greater risk of manifesting either skin or uveal melanoma (as well as other cancer types). In addition, oculo-dermal melanocytosis (overgrowth of melanocytes within the dermis of the skin in proximity to the eye), a rare condition also referred to as “nevus of Ota,” increase one’s risk of developing uveal melanoma.
There have been recent reports of families that harbor rare germline (inherited) mutations in BAP1 that make individuals within these families at greater risk of manifesting either skin or uveal melanoma (as well as other cancer types). In addition, oculo-dermal melanocytosis (overgrowth of melanocytes within the dermis of the skin in proximity to the eye), a rare condition also referred to as “nevus of Ota,” increase one’s risk of developing uveal melanoma.
New answer by ScottWoodmanMDPhD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
First, I will provide some background information on uveal melanoma. The uveal tract is comprised of the iris (the outer circular portion of the eye that we commonly associate with our “eye color”), ciliary body and choroid (portions of the eye that cannot be seen externally). Melanocytes, the melanin pigment producing cells within the uveal tract, can develop into uveal melanoma tumors. Because of their external nature, uveal melanomas of the iris can be observed without instrumentation as dark spots on the iris. Uveal melanomas that are isolated to the iris are very rare, have distinct genetics and are clinically less aggressive. About 95% of uveal melanomas involve the ciliary body and/or choroid, and are thus unable to be visualized without ophthalmologic instruments. Thus, when most people refer to uveal melanoma, they are referring to melanoma that arises in the ciliary body or choroid of the eye, and has a propensity to metastasize from the eye to other parts of the body in about 40-50% of cases.
In most cases, a person has no symptoms that indicate that they have uveal melanoma. Uveal melanoma is typically discovered as part of a routine eye exam in which the inner eye is visualized by an optometrist or ophthalmologist. However, symptoms that can be associated with uveal melanoma are a change in vision (blurriness, reduced acuity), increase pressure/pain. As such, there is no one symptom that is clearly associated with uveal melanoma, and for which one should watch. Regular eye exams and acting promptly if one has any troubling eye symptoms are prudent.
In most cases, a person has no symptoms that indicate that they have uveal melanoma. Uveal melanoma is typically discovered as part of a routine eye exam in which the inner eye is visualized by an optometrist or ophthalmologist. However, symptoms that can be associated with uveal melanoma are a change in vision (blurriness, reduced acuity), increase pressure/pain. As such, there is no one symptom that is clearly associated with uveal melanoma, and for which one should watch. Regular eye exams and acting promptly if one has any troubling eye symptoms are prudent.
New answer by ScottWoodmanMDPhD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
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