Hamartoma Syndromes

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

The book has an extensive glossary, that explains the meaning and relevance of medical terms appearing throughout the chapters. The glossary can be read as a stand-along document. Here is an example of one term, "hamartoma", excerpted from the glossary.

Hamartoma - Hamartomas are benign tumors that occupy a peculiar zone lying between neoplasia (i.e., a clonal expansion of an abnormal cell) and hyperplasia (i.e., the localized overgrowth of a tissue). Some hamartomas are composed of tissues derived from several embryonic lineages (e.g., ectodermal tissues mixed with mesenchymal tissue). This is almost never the case in cancers, which are clonally derived neoplasms wherein every cell is derived from a single embryonic lineage. Tuberous sclerosis is an inherited hamartoma syndrome. The pathognomonic lesion in tuberous sclerosis is the brain tuber, from which the syndrome takes its name. Tubers of the brain consist of localized but poorly demarcated malformations of neuronal and glial cells. Like other hamartoma syndromes, the germline mutation in tuberous sclerosis produces benign hamartomas as well as carcinomas, indicating that hamartomas and cancers are biologically related. Hamartomas and cancers associated with tuberous sclerosis include cortical tubers of brain, retinal astrocytoma, cardiac rhabdomyoma, lymphangiomyomatosis (very rarely), facial angiofibroma, white ash leaf-shaped macules, subcutaneous nodules, cafe-au-lait spots, subungual fibromata, myocardial rhabdomyoma, multiple bilateral renal angiomyolipoma, ependymoma, renal carcinoma, subependymal giant cell astrocytoma [62].

Another genetic condition associated with hamartomas is Cowden syndrome, also known as multiple hamartoma syndrome. Cowden syndrome is associated with a loss of function mutation in PTEN, a tumor suppressor gene. Features that may be encountered are macrocephaly, intestinal hamartomatous polyps, benign hamartomatous skin tumors (multiple trichilemmomas, papillomatous papules, and acral keratoses), dysplastic gangliocytoma of the cerebellum, and a predisposition to cancers of the breast, thyroid and endometrium.

I urge you to read more about my book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D. tags: rare disease, genetic disease, orphan disease, orphan drugs, types of cancer, tumor biology, rare cancers, hyperplasia, tissue overgrowth, carcinogenesis, glossary

Mosaic Variegated Aneuploidy Syndrome-1

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

The book has an extensive glossary, that explains the meaning and relevance of medical terms appearing throughout the chapters. The glossary can be read as a stand-along document. Here is an example of one term, "aneuploidy", excerpted from the glossary.

Aneuploidy - The presence of an abnormal number of chromosomes (for the species) in a cell. Most cancers contain aneuploid cells; an observation that holds true for virtually every poorly differentiated cancer. Aneuploidy is seen less often in benign tumors and well-differentiated tumors. Aneuploidy is also found in epithelial precancers and other growing lesions that can sometimes regress spontaneously (e.g., keratoacanthoma). These observations have prompted speculation that chromosomal instability and the acquisition of aneuploidy is an underlying cause of the cancer phenotype (i.e., tumor growth, invasion into surrounding tissues, and metastases).

Such causal associations invite skepticism, particularly in the realm of cancer biology, as virtually every cellular process and constituent of cancer cells has been shown to deviate from the norm. Nonetheless, there is good reason to suspect that aneuploidy is at least a factor in tumor development, as mutations that cause aneuploidy are associated with a heightened risk of cancer (e.g., Brca1 gene mutations [13] and mutations of mitotic checkpoint genes [14]). Cancer researchers have warned that aneuploidy, by itself, may not cause cancer [15]. Aneuploidy may need to be accompanied by other factors associated with genetic instability, such as the accumulation of DNA damage, specific cancer-causing mutations, epigenomic and cytogenetic abnormalities, and reduced cell death [15].

As usual, a rare disease helps to clarify the role of aneuploidy in carcinogenesis. Mosaic variegated aneuploidy syndrome-1 (MVA1) is caused by a homozygous or compound heterozygous mutation in the BUB1B gene, which encodes a key protein in the mitotic spindle check point. This disease is characterized by widespread aneuploidy in more than 25% of the cells of the body, and a heightened risk of developing childhood cancers (e.g., rhabdomyosarcoma, Wilms tumor, and leukemia). Because the underlying cause of mosaic variegated aneuploidy syndrome-1 is a gene that produces aneuploidy, and because such aneuploidy is an early event (i.e., congenital) that precedes the development of cancer and that is found in the developed cancer cells, then it is reasonable to infer that aneuploidy is closely associated with events that lead to cancer. See Mutator phenotype, Carcinogenesis, Cytogenetics, and Karyotype.

I urge you to read more about my book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D. tags: rare disease, common disease, orphan disease, orphan drugs, types of cancer, cancer types, tumor types, tumor biology, rare cancers, common cancers, aneuploidy, cytogenetics, euploidy, carcinogenesis, glossary

Virtually Every Type of Cancer is a Rare Cancer

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

Here is an excerpt from Chapter 8:

There are about 6000 types of cancer that have been assigned names by pathologists [4–6]. About a dozen of these cancers are common diseases. The remaining cancers (i.e., about 6000 entities) comfortably qualify as “rare” under U.S. Public Law 107-280, the Rare Diseases Act of 2002 [7]. Consequently, healthcare workers must somehow come to grips with 6000 types of rare cancers.

Moreover, the variety of rare cancers is increasing rapidly. As we learn more and more about the genetics of cancers, we find that the common cancers can be subtyped into genetically distinct groups. Furthermore, we are finding an increasing number of alternate alleles and heterogeneous genes that account for rare diseases.

Hence, the trend is leading us to divide the common cancers into genetically distinct subtypes that qualify as rare cancers, and to divide the known rare cancers into ultra-rare subtypes.

I urge you to read more about my book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D. tags: rare disease, common disease, orphan disease, orphan drugs, types of cancer, cancer types, tumor types, tumor biology, rare cancers, common cancers

Common Cancers Have Rare Cancer Subsets

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

One of the key ideas developed in the book is that each common diseases is actually an aggregate of cellular processes that are present, individually, in rare diseases. In the case of the common cancers, we can find specific rare diseases that are subsets of the common diseases.

Here is an excerpt from Chapter 8:

8.3.3 Inherited syndromes that cause rare cancers are often associated with increased risk for developing common cancers; hence, the causes of rare cancers are related to the causes of common cancers. Many of the greatest advances in our understanding of common cancers have come through the study of rare familial cancer syndromes in which common types of cancer occur. Here are a few common cancers and the familial syndromes that account for a small percentage of cases.

Colon tumors (benign and malignant)

- Colorectal cancer hereditary non-polyposis
- Polyposis syndrome, mixed hereditary
- Turcot syndrome (central nervous system cancer and familial polyposis of the colon)
- Mismatch repair gene pmsl1 colorectal cancer hereditary, non-polyposis type 3 included
- Checkpoint kinase 2 S. pombe homologue of breast and colorectal cancer susceptibility
- Colorectal adenomatous polyposis autosomal recessive
- Oligodontia–colorectal cancer syndrome
- Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
- Adenomatous polyposis of the colon (APC)
- Peutz–Jeghers syndrome
- Colorectal cancer hereditary non-polyposis type 2
- Colorectal cancer susceptibility on chromosome 9

Lung cancer

- Lung cancer 1
- Lung cancer, alveolar cell carcinoma included

Breast cancer

- Brca1 breast cancer type 1
- Breast cancer 11–22 translocation associated
- Brca2 breast cancer type 2
- Brca3 breast cancer type 3

Basal cell carcinoma of skin (see Glossary item, Basal cell carcinoma)

- Basal cell carcinomas with milia and coarse sparse hair
- Basal cell nevus syndrome
- Basal cell carcinoma, multiple
- Basaloid follicular hamartoma syndrome (see Glossary item, Hamartoma)
- Basal cell carcinoma with follicular differentiation
- Xeroderma pigmentosum complementation group b
- Xeroderma pigmentosum 1

Renal cell carcinoma

- Renal carcinoma, familial associated 1 included
- Renal cell carcinoma, papillary
- Non-papillary renal carcinoma 1
- Renal cell carcinoma, papillary 3
- Leiomyomatosis and renal cell cancer hereditary

Thyroid cancer

- Thyroid carcinoma, familial medullary
- Familial non-medullary thyroid cancer
- Papillary thyroid microcarcinoma
- Thyroid carcinoma, papillary with papillary renal neoplasia
- Thyroid carcinoma, non-medullary 1
- Thyroid carcinoma, Hürthle cell
- Thyroid carcinoma, follicular

Ovarian cancer

- Epithelial ovarian cancer
- Ovarian cancer, epithelial, susceptibility to

Melanoma

- Melanoma, cutaneous malignant 4
- Melanoma, cutaneous malignant 3
- Familial atypical multiple mole melanoma-pancreatic carcinoma syndrome
- Dysplastic nevus syndrome, hereditary b-k mole syndrome

Prostate cancer

- Prostate cancer, hereditary x-linked
- Prostate cancer, hereditary 1
- Prostate cancer, hereditary 20
- Prostate cancer, hereditary 7
- Prostate cancer, hereditary 3
- Prostate cancer/brain cancer, susceptibility

When we look at individual inherited cancer syndromes, we see that both rare and common cancers may result. Here is the list of different types of cancer associated with the Li–Fraumeni syndrome [15]. The syndrome-associated cancers are divided into common and rare cancers.

Common tumors associated with Li-Fraumeni syndrome

- Breast cancer
- Lung adenocarcinoma
- Colon cancer
- Pancreatic cancer
- Prostate cancer

Rare tumors associated with Li-Fraumeni syndrome

- Soft tissue sarcomas
- Osteosarcomas
- Brain tumors
- Acute leukemias
- Adrenocortical carcinomas
- Wilms tumor
- Phyllodes tumor of breast

It is worth noting that the common cancers associated with rare cancer syndromes have a similar morphologic appearance as their sporadic counterparts. This suggests that regardless of underlying genetic cause, the pathogenesis of each named common cancer tends to converge to its characteristic phenotype.

I urge you to read more about this book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D. tags: rare disease, common disease, orphan disease, orphan drugs, carcinogenesis, common cancers, rare cancers, cancer syndromes, familial cancer syndromes

Blog Posts on Rare Diseases and Orphan Drugs

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

Over the past several weeks, I've been writing to several different blog sites on the subject of rare cancers. Here is a list of my rare disease posts, with links:

Developing Diagnostic Tests for Common Diseases: Role of the Rare Diseases

Rare Diseases Account for Subsets of Common Diseases

Phenocopy Mimics of Rare Diseases: Lessons for the Common Diseases

Phenocopy Diseases: Their Relationship to Rare Diseases and Common Diseases

What Rare Diseases Teach Us About the Cellular Basis of Aging

What is the Fundamental Biological Process that Causes Aging?

Wrinkling and Sagging are Chronic Toxic Processes Not Directly Caused by Aging

Disease Complexity: Rare Diseases and Common Diseases

Case Reports of Rare Diseases Have General Value

When Rare Diseases and Common Diseases Converge to Same Clinical Picture

Rare Diseases and Common Diseases can Converge to the Same Clinical Conditions

Rare Disease Legislation in the U.S.

Definition of Rare Disease

Developing Diagnostic Tests for Common Diseases: Role of the Rare Diseases

Rare Diseases Account for Subsets of Common Diseases

Improving Clinical Trials by Focusing on Rare Diseases

Rare Diseases of Unknown Origin

Rare Diseases are Sentinels for the Common Diseases

Biological Differences between Rare Cancers and Common Cancers

Rare Diseases are Biologically Different from Common Diseases

Rare Cancers are Biologically Different from Common Cancers

Rare Cancers

Clinical Trials and Rare Diseases

Rules for the Rare Diseases

The Rationale for Funding Rare Disease Research

New Book Explains the Importance of Rare Disease Research

I urge you to read more about this book. There's a good preview of the book at the Google Books site. If you think that you and your colleagues may benefit from reading this book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D.

tags: rare diseases, orphan diseases, orphan drugs, funding opportunities, rare cancers, common diseases, complex diseases, clinical trials, rare disease organizations, disease advocates

Recent Posts on Rare Cancers and other Rare Diseases

This past week, I've been busy writing blogs on the topic of Rare Diseases. I'm hoping to generate some interest for my newly published book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases.

Here is the list of my rare disease posts, with links to blog sites:

Developing Diagnostic Tests for Common Diseases: Role of the Rare Diseases

Rare Diseases Account for Subsets of Common Diseases

Improving Clinical Trials by Focusing on Rare Diseases

Rare Diseases of Unknown Origin

Rare Diseases are Sentinels for the Common Diseases

Biological Differences between Rare Cancers and Common Cancers

Rare Diseases are Biologically Different from Common Diseases

Rare Cancers are Biologically Different from Common Cancers

Rare Cancers

Clinical Trials and Rare Diseases

Rules for the Rare Diseases

The Rationale for Funding Rare Disease Research

New Book Explains the Importance of Rare Disease Research

I urge you to read more about this book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D.

tags: rare cancers, rare neoplasms, rare diseases, orphan drugs, funding justification, funding for rare diseases, funding for orphan drugs, rare disease organizations