FA FAmily Newsletter - Fanconi Anemia Research Fund

24 Pages·2007·1.75 MB·English

FA F

Amily
N
ewslet ter
#41 A Semi-annual Publication of the Fanconi Anemia Research Fund, Inc. Spring 2007
Keynote Speaker
Addresses Cancer in
FA Patients
Maura Gillison, MD, PhD, Johns
Hopkins Kimmel Cancer Center,
th
began our 18 Annual Scientific
Symposium with a keynote address
on The Challenge of Squamous Cell
Carcinoma in Fanconi Anemia. She
noted a “remarkable increase” in head
and neck cancers (as well as esopha-
geal, cervical, and vulvar squamous
cell carcinomas) in the FA population
compared to the general population.
Smoking and drinking, the pri-
Researchers discuss poster presentations at Symposium
mary causes of head and neck can-
th
The 18 Annual Fanconi Anemia cer in the general population, were
causal factors in only a small minor-
Scientific Symposium
ity of FA patients. Chromosomal
A record two hundred twenty-six a member of the Fund’s Scientific continued on page 
researchers convened in Bethesda, Advisory Board. While this session
MD, from October 19 – 22, 2006 was designed for newcomers, it was
for the 18th Annual Fanconi Anemia attended by many experienced FA highlights
Scientific Symposium. Participants researchers and found to be invalu-
included scientists and clinicians able by all. New Fanconi Anemia Gene
from 15 countries and from 64 Maura Gillison, MD, Johns Discovered ........................................2
universities and institutes, including Hopkins Kimmel Cancer Center,
Genetic Patterns of FA
29 participants from the nearby NIH delivered the keynote lecture, The
Squamous Cell Carcinomas ..........3
institutes. Challenge of Squamous Cell Carci-
This year, for the first time, the noma in Fanconi Anemia. Forty-five
Donation of Tissue for FA
Symposium included a session enti- researchers made oral presentations Research: An Urgent Need ........10
tled Fanconi Anemia 101: A Sophisti- on subjects including gene discov-
cated Introduction to the Science and ery and regulation; carcinogenesis; Family News ..................................11
Medicine of Fanconi Anemia, bril- hematopoiesis, stem cell transplanta-
Fundraising .....................................18
liantly presented by Akiko Shimam- tion, and therapeutics; functions of
ura, MD, PhD, Children’s Hospital, FA proteins; and model organisms
Research Funded in 2006 ...........24
Boston, and Raymond Monnat, Jr., and cell-free systems. Sixty-eight
MD, University of Washington and
continued on page 
MedicAl News
Techniques for Early Detection
of Head and Neck Cancer
Petra Wilder-Smith, DDS, PhD, University of California at Irvine, dis-
cussed early cancer detection techniques that are under investigation in her
laboratory. The goal of her research is to develop a non-invasive approach for
detecting cancer precursors and oral cancer at the earliest stage possible, and
to enable regular screening of high-risk patients.
Oral cancer has one of the worst survival rates of all cancers because early
detection is difficult. Current diagnostic techniques require surgical biopsy
and often cannot identify early cancerous changes. If detected early, however,
oral cancer has a better survival rate than most cancers. Clinicians desperately
need new tools for early detection. Several approaches are currently under
investigation.
Petra Wilder-Smith, DDS, PhD
Wilder-Smith discussed three new methods that show promise:
• Optical coherence tomography (OCT) combined with optical Doppler tomography (ODT) can image below the
surface of the oral tissues, and can show structures at a level of detail resembling that obtained under a microscope.
• Under certain types of laser light, precancerous and cancerous tissues fluoresce (glow) differently than healthy
tissues. Pre-treatment of mouth tissues with chemical agents called photosensitizers can enhance this effect. Very
early precancerous changes invisible to the naked eye are detected using fluorescence techniques.
• Some types of laser microscope can be connected to a probe that allows direct imaging of surface and subsurface tissues.
This technique permits very early and accurate diagnosis of pathologies in tissues such as the lining of the mouth.
These new techniques can be combined to achieve effective and rapid screening, diagnosis, monitoring, and delin-
eation of oral cancer. Wilder-Smith will explore the usefulness of these tools for FA patients. ◆
New Fanconi Anemia Gene Discovered
Two research teams, one from the than one cancer. Cancers included
Vrije Universiteit (Free University) Wilms tumor (cancer of the kidney);
Medical Center, Amsterdam, The acute myelogenous leukemia; neu-
Netherlands, led by Johan de Winter, roblastoma (a cancer of the nervous
PhD, and another from the Institute system) and medulloblastoma (brain
of Cancer Research, Sutton, United tumor). Six patients died before the
Kingdom, led by Nazneen Rahman, age of four.
MD, PhD, announced the discovery Almost all cases of FA with solid
th
of the 12 Fanconi anemia gene, tumors in early childhood that Rah-
PALB2/FANCN.* Like BRCA2/ man and colleagues have studied are
FANCD1, PALB2/N functions caused by mutations in either the
downstream of the FANCD2 path- BRCA2 or PALB2 genes.
way, and disease mutations in this In her recently published paper
gene cause a very severe phenotype. in Nature Genetics (February 2007),
Rahman described seven FA Rahman writes that carriers of
patients with mutations in this rare PALB2 mutations have a two-fold
complementation group. All seven increased risk of breast cancer.
patients had developed cancer early *The designation PALB2 means
Johan de Winter, PhD in childhood, and three had more “partner and localizer of BRCA2.” ◆
 FA Family Newsletter
Genetic Patterns of FA Squamous Cell Carcinomas
and a Non-Invasive Screening Technique
Ruud Brakenhoff, PhD, Vrije by precursor lesions. Only 20% of
Universiteit (Free University) Medi- these lesions are visible to the naked
cal Center, Amsterdam, presented eye; 80% are identified by biopsy
data on his analysis of 15 tumors, and careful examination of tissues for
taken from 14 FA patients ages 13- genetic alterations.
44. Ten malignancies were from the Taking biopsies of suspicious tis-
head and neck; two were from the sues is painful for the patient and not
esophagus; and three were from the ideal for identifying and monitoring
anogenital area. Brakenhoff ana- precursor lesions. Brakenhoff has
lyzed the patterns of genetic changes developed a new, non-invasive way to
and presence of the human papil- screen for these lesions. Using a small
loma virus (HPV) and made several brush, he removes superficial cells
important observations. from different places in the mouth.
The genetic patterns found in FA These are then studied for suspicious
tumors are similar to those found genetic re-arrangements. The test is
in tumors from the non-FA popula- validated by analysis of samples from
Ruud Brakenhoff, PhD
tion. Of nine tumors analyzed, seven non-FA patients with leukoplakia and
showed a mutation in the p53 gene. healthy non-cancer controls. When 22 FA patients have been analyzed;
Only two of the 15 tumors were genetic changes were found in leuko- 9 FA patients had genetic alterations
positive for HPV. This finding sug- plakia biopsies, they were also found in in one or more of the samples. This
gests that HPV plays a less promi- the brushed samples from these same method might provide a non-inva-
nent role in FA cancers than was patients. In the healthy non-cancer sive, painless method to screen for
suggested by an earlier study. We controls, no changes were found. genetic changes that indicate a need
don’t yet know what might account Brakenhoff has obtained samples for increased surveillance or treat-
for this difference. from 75 French and German FA ment, even when visible changes have
Head and neck cancer is preceded patients. To date, samples taken from not yet developed. ◆
FA Patients with Mutations in BRCA2/FANCD1
Have Severe Phenotype; Carriers Also At Risk
Blanche Alter, MD, MPH, have cancer. The risk of malignancy
National Cancer Institute, presented was 66 times higher than in other FA
data on 27 FA patients defective in patients. The cumulative probability
BRCA2/FANCD1. This group is of any cancer was 97% by age 5.
unique in the severity of the physical Certain mutations were associ-
phenotype, and in very early onset ated with cancer in this population.
and high rates of leukemia and spe- Patients with an IVS7 mutation
cific solid tumors. were at exceedingly high risk for
Ten patients had acute myeloid leukemia; those with an 886delGT
leukemia (AML), and four developed or 6174delT were at high risk for a
acute lymphocytic leukemia (one brain tumor.
of these had AML as well). Twelve Carriers of a BRCA2 mutation Blanche Alter, MD, MPH
patients had brain tumors, seven were at risk for breast cancer. Of 21
developed a Wilms tumor (a cancer families studied, 11 had a family for carriers of a BRCA2 mutation,
found in the kidney), and one pre- member with breast cancer. In all, 28 Alter advised that these families seek
sented with neuroblastoma. Only relatives in these families had breast genetic counseling and appropriate
two patients, ages 2 and 30, did not cancer. Given the increased risk medical surveillance. ◆
spring 007 
Questions and Answers FA Complementation
about the Human Papillomavirus Analysis Available
by Lynn Frohnmayer, with a little help from Google Cincinnati Children’s Hospital
Medical Center (CCHMC) has
What is the Human Papillomavirus (HPV)? received an NIH award to supple-
HPV is an extremely contagious and common virus. It is called “papil- ment the costs of testing for FA
lomavirus” because papilloma means “wart,” and this virus can cause warts. complementation groups. Comple-
There are around 100 different types of HPV. Sixty of these are benign or can mentation analysis is now available
cause warts on non-genital skin, primarily of the hands and feet. to clinicians and researchers for $150
per sample. An additional charge of
What is the relationship between HPV and sexual contact? $180 is added to establish cell lines
Thirty to forty types of HPV are spread primarily through skin-to-skin from peripheral blood or skin biop-
sexual contact, and are called genital HPVs. Genital HPV is extremely com- sies, if necessary. Cincinnati also pro-
mon in the sexually active population. It is spread through vaginal, anal and vides instructions for participation
oral sex or any skin-to-skin genital contact. Every year, approximately 6.2 in the International Fanconi Anemia
million Americans are newly infected with genital HPV, and at any one time, Registry (IFAR) of The Rockefeller
20 million Americans have genital HPV. Approximately 75%-80% of those University, which facilitates subse-
who have EVER been sexually active during their lifetimes will have had quent mutation identification.
HPV at some point. Complementation group analy-
sis is currently available for eight
Why should we be concerned about HPV? complementation groups, which
Most of the time, HPV goes away on its own, eliminated by our immune represent greater than 90% of the FA
systems. Most people are unaware they were ever infected with HPV. How- patients in the US. Complementa-
ever, the virus can also stay in the body and cause worrisome problems. Geni- tion analysis, including the estab-
tal HPVs are divided into two categories: high-risk and low-risk. High-risk lishment of cell lines, may require
HPVs can cause cancer; low-risk can cause genital warts. up to six months. Established cell
lines will be deposited in the FA Cell
HPV and Cancer Repository at CCHMC, and will be
Twelve to fifteen types of HPV cause or are associated with cancer. Nearly provided to researchers with proto-
100% of cervical cancer is caused by HPV. Two types in particular, HPV 16 cols approved by their Institutional
and 18, cause 70% of cervical cancer. In the United States, almost 10,000 Review Board.
women are diagnosed with cervical cancer annually, and approximately 4,000 Contact Dr. David A Williams
die from this disease. Cervical cancer grows slowly and is preceded by pre- ([email protected], 513-
cancerous cells. Precancerous cells usually go away on their own. These cells 636-0364) or Lilith Reeves (lilith.
can be monitored through Pap smears and removed if they persist or evolve. [email protected], 513-636-3468)
Risk is not limited to cervical cancer. HPV is strongly implicated in anal for more information or to schedule
cancer and is also found in cases of vaginal and vulvar cancer. Approximately testing. ◆
20-25% of cases of head and neck cancer in the general population test posi-
tive for HPV.
Use of logo
HPV and Genital Warts
Over 500,000 new cases of anogenital warts are diagnosed yearly in the A reminder to our FA families:
US. Ninety percent of these are caused by HPV types 6 or 11. Warts often please use our logo or letterhead
appear in clusters but can appear as single warts. They may cause itching, only after you have consulted the
staff of the FA Research Fund and
burning, or general discomfort. They can be removed by freezing or burn-
received their approval. This step is
ing, using an acid applied by a physician or by an expensive self-administered
necessary to be sure our messages
cream. Eliminating the warts can take a long time, and they can return as
are accurate and consistent and
long as the HPV virus that caused the warts is still present.
helps to avoid legal complications.
We are happy to collaborate on
continued on page 1 fundraisers and mailings.
 FA Family Newsletter
Centers Plan Studies of HPV Vaccine in FA Patients
The National Cancer Institute not to wait for vaccine through the vaccine if they are included in the
(NCI) is planning a five-site study study, they can receive the vaccine FDA-approved population (females
of the safety and effectiveness of the from their local physicians (vaccine ages 9–26). The patient’s family or
HPV vaccine in FA patients. Partici- will NOT be free) and still enroll insurance company will be billed.
pating centers are the University of within four weeks of completing Patients not wishing to partici-
Minnesota Medical Center; Oregon vaccination to be monitored for pate in a clinical study can obtain
Health & Science University; Uni- immune response. the HPV vaccine through their local
versity of California in Los Angeles; Cincinnati Children’s Hospital physician or health center. Three
and Stanford University. NCI plans Medical Center will also study the inoculations are required, at a cost
to begin this study in April 2007. FA safety and effectiveness of the HPV of approximately $125- $150 per
patients age nine and above, male vaccine. This will be linked to a com- injection. Since this vaccine has only
and female, can enroll. Transplanted prehensive evaluation of the immune been approved for females ages 9-
patients must wait at least one year status of FA patients. The study is 26, check with your physician about
post-transplant to be included in this ready for submission to regulatory vaccinating anyone outside of these
study. Patients who participate in and review bodies. Cincinnati may parameters. For all patients, confer
this study, receive their three shots or may not receive the vaccine at with your insurance company about
at one of the above centers, and no charge for those participating in possible coverage.
agree to participate in a series of the study, so patients may be billed. A federal program called Vaccines
clinical visits will receive the vac- Patients who do not wish to be part for Children will defray much of
cine free of charge. If patients prefer of this study can still obtain the continued on page 
Keynote Speaker Addresses malignancies found HPV in only two to be safe and effective in the general
Cancer in FA Patients cancers. These different outcomes are population for cervical cancer pre-
currently the focus of investigation. vention. The ability of the vaccine to
continued from page 1
Gillison noted that HPV is involved prevent oral HPV infection, however,
instability, which defines FA, is a in almost 100% of cases of cervical is unknown. ◆
strong risk factor. Other factors that cancer. The HPV vaccine, which
increase risk of head and neck cancer prevents the two types of HPV (16
in the general population may also and 18) that cause 70% of cervical
apply to the FA patient, including cancers, is remarkably effective in
poor dental hygiene and diets low preventing this complication.
in fruits and vegetables. The risk of Gillison recommends FA patients
head and neck cancer among patients obtain regular screening (at least
with FA increases with age. The risk annually) for head and neck cancer
is further increased by bone mar- by a board-certified head and neck
row transplant because of exposure surgeon (not a dentist). Based on
to chemotherapy, radiation therapy, literature reports of earliest presenta-
and immunosuppressive drugs as well tion of head and neck cancer in FA
as complications such as acute and patients, screening should begin at
chronic graft-versus-host disease. age 10-12 or starting one year after
Gillison discussed the possible bone marrow transplant, whichever
role of the human papillomavirus occurs first. Patients with FA can be
(HPV) in FA cancers. In one study long-term survivors of their cancer if
of 33 FA patients with cancer, 25 it is caught at an early stage that can
patients or 83% were positive for be treated by surgical therapy alone.
HPV. Specific sites of these cancers In addition, FA patients should
were head and neck (19), vulva (5) consider immunization against the
and anus (1). Another study of 15 FA HPV virus, which has been shown
Maura Gillison, MD, PhD
spring 007 
Thymic Shielding Reduces Infection after
Alternate Donor Transplants
Researchers at the University of this population. Researchers exam-
Minnesota continue to modify their ined whether shielding the thymus
transplant protocol in an effort to gland from radiation would hasten
improve outcomes for FA patients immune recovery, decrease infections
receiving alternate donor bone mar- and improve outcomes.
row transplants. At the present time, Margaret MacMillan, MD, pre-
toxicity related to the conditioning sented results of an April 2004–June
regimen and infections are the major 2006 trial of 16 FA patients who
obstacles to successful transplant in received thymic shielding in addi-
tion to the regular alternate donor
protocol. Researchers compared
outcomes to 43 previously trans-
planted FA patients who had received
the same protocol without thymic
shielding. Of the 16 patients in the Margaret MacMillan, MD
new trial, 15 engrafted (one did not
survive long enough to be evalu- those receiving thymic shielding
ated). Patients who received thymic experienced a faster rate of recovery
shielding had a total of 9 infections: of infection-fighting blood cells.
4 bacterial, 3 viral and 2 fungal. The It also appears that overall survival
43 patients without thymic shielding improved in the cohort of patients
experienced a total of 126 infections: receiving thymic shielding (79%),
68 bacterial, 37 viral and 21 fungal. although the number of patients is
Infections were significantly lower in small and the time post-transplant
the shielded population. In general, short. ◆
Dr. Bing Xia receives award for Best Basic Minnesota Reduces Radiation Dose in Alternate
Science Poster Abstract.
Donor Transplants
th
The 18 Annual Fanconi Anemia
University of Minnesota trans- Once 10 patients have been
Scientific Symposium
plant physicians are testing new pro- enrolled and have engrafted, the radi-
continued from page 1
tocols in an effort to decrease toxicity ation dose will be decreased to 150
researchers presented posters on FA and reduce the risk of opportunistic rads. If 10 patients do well at this
research. At the Symposium Dinner, infections in patients undergoing dose, the next group of patients will
awards for the poster presentations bone marrow transplantation. Mar- receive no radiation. It is anticipated
were made by Dave Frohnmayer, garet MacMillan, MD, has designed that this approach will continue to
co-founder of the Fund, to the fol- a new radiation dose de-escalation speed immune reconstitution and
lowing recipients: Sheila Mohan, protocol for patients undergoing decrease the risk for opportunistic
PhD, Apollo Hospital, Chennai, alternate donor transplants. The pro- infections. In addition, eliminating
India for Best Clinical Abstract; tocol includes thymic shielding, but radiation may reduce the risk of later
Bing Xia, PhD, Dana-Farber Cancer decreases radiation from 450 rads to malignancies. Other future trials to
Institute, Boston for Best Basic Sci- 300 rads. improve survival include the use of
ence Abstract; and Mohammed-Reza To date, eight patients have multipotent adult stem cells at the
Saadatzadeh, PhD, for Best Transla- enrolled in this trial. All eight have time of transplant. ◆
tional Abstract. ◆ engrafted and are alive and well. [We regret to report that one of the eight
patients in the reduced radiation regimen has
subsequently passed away. Eds]
 FA Family Newsletter
Cancer Prevention in Fanconi Anemia
Bone marrow failure and malig- The difference between the treat-
nancies both greatly shorten the life ed and untreated FA mice was very
span of FA patients. Bone marrow significant. Both groups developed
transplantation is currently the only the same kinds of malignant tumors,
curative therapy for the bone marrow but mice treated with tempol lived
problems that affect FA patients, but 30% longer than untreated mice
transplantation still leaves patients (414 days compared to 332 days,
at risk for cancer. Markus Grompe, respectively). By the time the first
MD, Oregon Health & Science Uni- tempol-treated mice developed an
versity and his colleagues are using epithelial cancer, 60% of the untreat-
mouse models of FA to test various ed mice had already died. A notice-
therapeutic interventions that may able side effect was weight loss of 15–
reduce malignancies or delay the 20% in the mice treated with tempol
onset of these tumors. regardless of whether they had FA
Using a strain of FA mice that or not. Additional testing, however,
usually develop epithelial tumors indicates that tempol does not harm
at about one year of age, Grompe FA hematopoietic stem cells.
tested whether tempol, an oxygen Grompe is testing additional com- Markus Grompe, MD
radical scavenger, might delay tumor pounds to identify the most promis-
formation. Twenty FA mice were ing candidates for clinical trials. ◆
treated with tempol; twenty FA mice
received no treatment. Non-FA mice
were used as controls.
Cigarette Smoke Concentrate Toxic to Cells Centers Plan Studies of HPV
Vaccine in FA Patients
Laura Hays, PhD, Oregon Health & Science University Cancer Institute,
continued from page 
studied the effect of cigarette smoke condensate (CSC) on human bronchial
epithelial cells and on both normal the cost of this vaccine for eligible
and FA mouse epithelial cells to patients. Patients must meet FDA
learn how CSC affects the FA path- guidelines and be 18 or younger,
way. Her study revealed that CSC Medicaid eligible or uninsured (or
is extremely toxic and that FA cells have insurance which does not cover
are more sensitive to cigarette smoke this vaccine), or qualify as American
than normal cells. In fact, CSC Indian or Alaskan Native. Call your
caused 25% more death in FA cells. local health department for addition-
CSC also induced a high num- al information on eligibility require-
ber of chromosomal breaks in FA ments.
cells, and suppressed the expression For contact information concern-
of the Fanconi anemia pathway in ing the above study centers, please
normal cells. FA patients are at high contact Jana Black, Family Support
risk for cancer of the head and neck. Coordinator, at [email protected] or
In light of these results, Hays con- at 541-687-4658. ◆
cluded that cigarette smoke, includ-
ing second-hand smoke, would
create an extraordinary problem for
FA patients. She strongly recom-
mended that FA patients should not
be exposed to first or second-hand
cigarette smoke. ◆ Laura Hays, PhD
spring 007 7
Dave Frohnmayer welcomes participants to the Small Molecule Meeting
Small Molecule Testing Workshop
th
At our 18 Annual Scientific of Health. Participants noted that FA proteins and the various path-
Symposium in Bethesda, Maryland, three available FA models—zebrafish, ways that interact with FA genes.
Markus Grompe, MD, Oregon frogs, and mice—can all show the In the meantime, living FA patients
Health & Science University, rein- FA phenotype. They agreed to col- need better therapies immediately.
forced the belief of a number of laborate on an effort to test if exist- These scientists suggest that small
experts that the FA research commu- ing FDA-approved compounds can molecule studies may yield positive
nity should begin testing small mol- improve the FA phenotype in these results before the molecular basis of
ecule compounds in FA animal mod- animal models. FA is fully understood. We are heart-
els. These scientists believe there is a Significant time will be required ened by their willingness to test this
chance that an already known com- to understand the function of all the hypothesis. ◆
pound might correct or delay onset
of serious problems. For example,
Grompe has shown that the antioxi-
dant compound, tempol, delays the
onset of tumors in FA mice. Experts Mark Your calendar
have suggested first testing drug
compounds in zebrafish or frogs. Regional Meeting:
Compounds found to be potentially
FA comprehensive care center
therapeutic should then be tested in
mouse models, with human FA trials the University of Minnesota
to follow.
Medical center & campus
Fifteen scientists convened on
February 12 in Portland, Oregon, to saturday, May 19, 007
brainstorm and share expertise per-
tinent to testing of small molecule
Please join us, regardless of whether you live in this particular
compounds. Scientists represented
geographic region. The meeting is open to all FA parents and adult
FA research, pharmaceutical compa-
FA patients over age 15. Scholarships are available. To register,
nies, laboratories developing and test-
contact Jana Black at 1-888-FANCONI or [email protected].
ing small animal models of human
diseases, and the National Institutes
 FA Family Newsletter
FA Regional Meeting in Cincinnati
Ten FA families from as far away
as Arizona attended the FA Regional
Meeting at Cincinnati Children’s
Hospital Medical Center (CCHMC)
on Saturday, February 24, and
Sunday, February 25.
Families were treated to presenta-
tions from the physicians, research-
ers, and staff of the FA Comprehen-
sive Care Center. David Williams,
MD, presented on three topics: the
biology of Fanconi anemia; stem
cell collection and gene therapy; and
complementation group testing and
mutation identification. Susan Rose,
MD, discussed endocrine issues,
including the progress of her clini-
cal trial on thyroid function in FA
patients. Stella Davies, MBBS, PhD,
and Richard Harris, MD, spoke on Families enjoyed watching divers with sharks at the Newport Aquarium.
blood and marrow transplants for
FA, and Dr. Davies presented as well the hands and arms of FA patients. discussed the support services offered
on her clinical trial on the use of Arleen Auerbach, PhD, from The by Cincinnati Children’s to FA
Etanercept for the treatment of bone Rockefeller University, New York, patients and their families.
marrow failure. Frank Smith, MD, presented information on prenatal The attendees were heartened by
discussed the use of low dose andro- genetic testing, pre-implantation the hospital’s emphasis on research
gens, and Thomas Kiefhaber, MD, genetic diagnosis, and in vitro fertil- into Fanconi anemia. They had the
presented information on surgery for ization. Robin Mueller, RN, BSN, opportunity to meet and talk with
thumb and radial abnormalities in and Andrea Houchen, MSW, LCW, FA researchers Qishen Pang, PhD,
Ruhikanta Meetei, PhD, Susanne
Wells, PhD, and Paul Andreassen,
PhD.
On Saturday, the hospital spon-
sored an evening at the Newport
Aquarium, where families were
treated to an excellent dinner and an
opportunity to socialize while enjoy-
ing the Aquarium exhibits and shows.
Judging from the evaluations
completed by the attendees, the fami-
lies greatly appreciated this meeting.
The comment from one family was
echoed by all: “The meeting was
wonderful. As usual, the CCHMC
went all out to make the visit as
comfortable as possible.” ◆
Frank Smith, MD, discusses Cincinnati’s oxandrolone clinical trial
spring 007 9
Mosaicism and Clinical Outcomes in FA
Jakub Tolar, MD, PhD, Uni- to have marrow progenitor cell
versity of Minnesota, discussed the mosaicism. Of the 12 with marrow
relationship between mosaicism and mosaicism, only six were also mosaic
clinical outcome in FA patients. in the blood. Of these six patients
Mosaicism in FA means that two with mosaicism in both the blood
populations of cells are present, one and marrow, four had normal blood
with the FA defect and one without. counts and two had severe bone
The question is whether the presence marrow failure. Remarkably, of the
of mosaic cells in the blood predicts remaining six that were mosaic only
mosaicism in the marrow and wheth- in the bone marrow, 5 had marrow
er mosaicism has any impact on the failure. Of 4 that were mosaic only in
clinical course in patients with FA. the blood lymphocytes, only one had
Forty-two consecutive FA patients marrow failure thus far.
referred to the University of Min- Tolar concluded that mosaicism
nesota were evaluated for mosaicism may be more common than previ-
Jakub Tolar, MD, PhD
in the blood lymphocytes and mar- ously recognized. While it is clear
row progenitor cells. Ten patients that mosaicism does not protect FA
were found to have blood lympho- patients from developing marrow follow-up are needed to fully under-
cyte mosaicism and 12 were found failure, additional patients and longer stand its significance. ◆
Donation of Tissue for FA Research: An Urgent Need
The Fund urgently wishes to National Institutes of Health and researchers worldwide who are seek-
expedite research into Fanconi ane- from the NIH Office of Rare Dis- ing human tissue samples. NDRI
mia, particularly into the squamous eases to provide researchers with the matches donors with appropriate
cell cancers (SCC) that affect so necessary materials to research rare requests and then sends the samples
many patients. To do that, we ask for diseases. directly to that researcher. Personal
your help in establishing a collection The donation of research materi- details of the donor remain strictly
of tumor tissue samples and related als (such as biopsy material or tumor confidential, and no donor informa-
medical records so that FA research- tissue from head and neck cancer) tion is given to the scientists.
ers can conduct their research. As through NDRI is designed to be If a patient is diagnosed with
you know, FA is a very rare disease. simple and sensitive to donors and SCC or needs a biopsy, the natu-
The number of FA patients who have donor families. Potential donors ral focus is on that urgent medical
biopsies of possible squamous cell will receive a packet of information need. NDRI therefore encourages
tumors or have these tumors surgi- describing the donation process and prior enrollment, months or even
cally removed is very small. Thus, we consent forms. Donations of tumor years in advance, so that a patient’s
ask that each such patient consider or biopsy material are made at no information is on record and ready
donating tissue samples for FA cost to the donor, except the cost of should the need for a biopsy or
research. a blood draw if that is required for surgery arise. NDRI would then be
To facilitate tumor sample col- a particular research project. The able to contact your physician prior
lection, the Fund has entered into a NDRI will work with your sur- to the procedure and obtain your tis-
partnership with the National Dis- geon or physician so that the tissue sue donation without delay.
ease Research Interchange (NDRI). can be obtained at the time of the For more information or assis-
NDRI is a non-profit organization procedure. tance in donating tissue, contact Jana
with 25 years experience in obtain- NDRI follows strict governmental Black, Family Support Coordinator
ing, storing and distributing human regulations and guidelines regarding at 1-888-FANCONI or jana@fan-
cells, tissues and organs to research- donor consent and confidentiality; coni.org. To contact NDRI directly,
ers and scientists (www.ndriresource. tissue samples are provided only to contact Mike Keough, NDRI Private
org). NDRI receives funding for approved biomedical researchers. Donor Manager, at 1-800-222-6374
its Rare Disease Program from the NDRI has a large database of or [email protected]. ◆
10 FA Family Newsletter