Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
2002-01-04
2004-08-31
Benzion, Gary (Department: 1634)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S091100, C435S091200, C536S023100, C536S024300, C536S025320
Reexamination Certificate
active
06783944
ABSTRACT:
BACKGROUND OF THE INVENTION
The melanocyte can give rise to a number of morphologically different tumors. Most of them are biologically benign and are referred to as melanocytic nevi. Examples of melanocytic nevi are congenital nevi, Spitz nevi (including pigmented spindle cell nevi, which are regarded as a subtype of Spitz nevi), dysplastic or Clark's nevi, blue nevi, lentigo simplex, and deep penetrating nevus.
Patients with congenital melanocytic nevi (CMN) have an increased risk of developing melanoma. Whereas in small—(<1.5 cm) and intermediate-sized CMN (1.5-20 cm) the risk seems to be low (Rhodes, A. R.,
Med Clin North Am.,
70:3-37 (1986); Sahin, S. et al.,
J Am Acad Dermatol.,
39:428-33 (1998)), large CMN (>20 cm) carry a 5-15x times increased future risk to develop melanoma and rarely, other neural crest derived malignancies ((Swerdlow, A. J. et al.,
J Am Acad Dermatol.,
32:595-9 (1995); Ruiz-Maldonado, R. et al.,
J Pediatr.,
120:906-11 (1992); Quaba, A. A. and Wallace, A. F.,
Plast Reconstr Surg.,
78:174-81 (1986); Gari, L. M. et al.,
Pediatr Dermatol.,
5:151-8 (1988); Egan, C. L. et al.,
J Am Acad Dermatol.,
39:923-32 (1998); Bittencourt, F. V. et al.,
Pediatrics,
106:736-41 (2000); DeDavid, M. et al.,
J Am Acad Dermatol.,
36:409-16 (1997); Marghoob, A. A. et al.,
Arch Dermatol.,
132:170-5 (1996)).
Melanoma refers to malignant neoplasms of melanocytes. Its proper diagnosis and early treatment is of great importance because advanced melanoma has a poor prognosis, but most melanomas are curable if excised in their early stages. Although, in general the histopathological diagnosis of melanoma is straightforward, there is a subset of cases in that it is difficult to differentiate melanomas from benign neoplasms of melanocytes, which have many variants that share some features of melanomas (LeBoit, P. E. Stimulants of Malignant Melanoma: A Rogue's Gallery of Melanocytic and Non-Melanocytic Imposters, In
Malignant Melanoma and Melanocytic Neoplasms
, P. E. Leboit, ed. (Philadelphia: Hanley & Belfus), pp. 195-258 (1994)). Even though the diagnostic criteria for separating the many simulators of melanoma are constantly refined, a subset of cases remains, where an unambiguous diagnosis cannot be reached (Farmer et al., Discordance in the Histopathologic Diagnosis of Melanoma and Melanocytic Nevi Between Expert Pathologists,
Human Pathol.
27: 528-31 (1996)).
During the neonatal period several types of melanocytic tumors can develop within CMN, many of which are thought to be distinct from melanoma (DeDavid, M. et al.,
J Am Acad Dermatol.,
36:409-16 (1997)). These can be small to large, occasionally involving up to 50% of the trunk, and can grow very fast and ulcerate (Clark, W. H. et al.,
Pathology of the Skin,
1st edition, pp. 729-35, New York, McGraw-Hill (1990)). Most of these tumors have a benign course and tend to regress after a period of rapid growth. However, because true melanoma can occur in the neonate, the development of any secondary proliferation in a CMN is of significant concern.
These lesions can be extremely difficult to classify histologically. Four different histological patterns of proliferations in CMN during the neonatal period have been described (Clark, W. H. et al.,
Pathology of the Skin,
1st edition, pp. 729-35, New York, McGraw-Hill (1990)): 1) simulants of superficial spreading melanoma, in which the epidermis and superficial dermis contain large epitheloid melanocytes, sometimes with pagetoid spread in the epidermis; 2) simulants of nodular melanoma with a nodular proliferation of large melanocytes with uniform nuclei in the dermis; 3) cases described as “proliferative neurocristic hamartoma”, characterized by a deep dermal or subcutaneous proliferation with a variety of forms of neural or mesenchymal differentiation; and 4) true melanoma, most of which show small blast-like melanocytes with hyperchromatic nuclei, scant cytoplasm and a high mitotic rate.
The current invention is based on the discovery that chromosomal aberrations are common in atypical nodular proliferations and further, are absent from conventional congenital nevi. The aberrations are predominantly numerical changes, in contrast to those identified in melanoma, in which structural chromosomal aberrations are found in the vast majority of cases. These findings are useful in the classification of histopathologically ambiguous cases.
BRIEF SUMMARY OF THE INVENTION
The current invention provides a method of typing a growth arising in association with a congenital nevus, the method comprising providing a skin tumor sample from a patient and detecting a change in chromosome number in a nucleic acid sample from the skin tumor sample. The change in chromosome number is typically a gain of chromosome 10, a gain of chromosome 11, or a loss of chromosome 7. The presence of one or more of these changes in the skin tumor sample types a lesion as a benign growth. Similarly, the absence of changes in chromosomal aberrations that are frequently associated with melanoma, types the skin tumor sample as a benign growth.
In one embodiment, the detection step comprises contacting a nucleic acid sample from the patient with a probe which selectively hybridizes to a target polynucleotide sequence on a chromosome selected from the group consisting of chromosome 10, chromosome 11, and chromosome 7; wherein the probe is contacted with the sample under conditions in which the probe binds selectively with the target polynucleotide sequence to form a stable hybridization complex; detecting the formation of the hybridization complex; and detecting a change in chromosome number, the change selected from the group consisting of a gain of chromosome 10, a gain of chromosome 11 and a loss of chromosome 7.
The nucleic acid sample can be, for example, an interphase nucleus or a metaphase cell. The probe is often labeled with a fluorescent labeled, but can also be labeled with other labels such as digoxigenin or biotin. Often, the probe is bound to a solid substrate and further, can be a member of an array. In some embodiments, the probe is a centromeric probe.
The methods of the invention can also comprise a further step of contacting the nucleic acid sample with a reference probe that binds selectively to a chromosome that does not undergo changes in chromosome number in these lesions. Such reference probes include, e.g., probes to chromosomes 1, 2, 4, 12, 13, 14, and 19.
Additionally, the methods of the invention can comprise a step of blocking the hybridization capacity of repetitive sequences in the nucleic acid sample. For example, unlabeled blocking nucleic acids such as comprising repetitive sequences, such as Cot-1 DNA, are contacted with the sample.
Definitions
To facilitate understanding the invention, a number of terms are defined below.
The terms “melanoma” or “cutaneous melanoma” refer to malignant neoplasms of melanocytes, which are pigment cells present normally in the epidermis and sometimes in the dermis. There are four types of cutaneous melanoma: lentigo maligna melanoma, superficial spreading melanoma (SSM), nodular melanoma, and acral lentiginous melanoma (AM). Melanoma usually starts as a proliferation of single melanocytes at the junction of the epidermis and the dermis. The cells first grow in a horizontal manner and settle an area of the skin that can vary from a few millimeters to several centimeters. As noted above, in most instances the transformed melanocytes produce increased amounts of pigment so that the area involved can easily be seen by the clinician.
The term “melanocytic neoplasm” refers to an accumulation of melanocytes that can undergo a benign, locally aggressive, or malignant course. “Melanocytic neoplasm” encompasses both benign melanocytic neoplasms, “nevi”, and malignant melanocytic neoplasms, “melanoma”.
“Congenital melanocytic nevi” refer to moles that are present at birth or arise shortly thereafter. Often, such nevi can grow rapidly. Rapidly growing nodules occasionally arise in these nevi during the neonatal period. Hist
Benzion Gary
Goldberg Jeanine
The Regents of the University of California
Townsend and Townsend / and Crew LLP
LandOfFree
Genetic changes in atypical nodular proliferations in... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Genetic changes in atypical nodular proliferations in..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Genetic changes in atypical nodular proliferations in... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3361348