A 24-year-old woman comes to the office after discovering a new mole on her right leg. She is worried that it might be skin cancer as she has used tanning beds several times a year since age 18. Physical examination shows a 5-mm brown, oval macule on her anterior thigh with a homogeneous coloration and discrete borders. The lesion appears darker than her other moles. A biopsy of the lesion shows normal-appearing nevus cells clustered in the epidermis, and she is diagnosed with a benign acquired melanocytic nevus. During histologic analysis, her epithelial cells are each found to contain a condensed body composed of heavily methylated DNA at the periphery of the nucleus. This region of DNA is most likely associated with which of the following genetic findings?

Question

A 24-year-old woman comes to the office after discovering a new mole on her right leg.  She is worried that it might be skin cancer as she has used tanning beds several times a year since age 18.  Physical examination shows a 5-mm brown, oval macule on her anterior thigh with a homogeneous coloration and discrete borders.  The lesion appears darker than her other moles.  A biopsy of the lesion shows normal-appearing nevus cells clustered in the epidermis, and she is diagnosed with a benign acquired melanocytic nevus.  During histologic analysis, her epithelial cells are each found to contain a condensed body composed of heavily methylated DNA at the periphery of the nucleus.  This region of DNA is most likely associated with which of the following genetic findings?

Quizplus · Accepted Answer

11ec160b_3764_b26a_9249_6175c18dde88_MD0001_00 In genetically normal (46,XX) females, one X chromosome is normally randomly deactivated in each cell during early embryonic development. X-inactivation (lyonization) is maintained across cell division, resulting in clusters of cells throughout the body that express either the maternal or paternal X chromosome. This mosaic pattern of X-chromosome expression generally prevents X-linked recessive conditions from manifesting in female carriers. However, in rare cases, skewed lyonization (uneven inactivation of maternal/paternal X chromosome due to chance alone) may result in females developing an X-linked recessive condition (eg, classic hemophilia). The process of lyonization converts the inactive X chromosome into condensed heterochromatin, which can be identified on microscopy as a compact body at the periphery of the nucleus (Barr body). Heterochromatin consists of heavily methylated DNA (eg, cytosine converted to methylcytosine) and deacetylated histones, which cause it to have a low level of transcriptional activity (Choice C). A small proportion of genes remain transcriptionally active on the inactivated X chromosome. For this reason, inheritance of an abnormal number of X chromosomes can cause clinical manifestations due to a gene-dosage effect, as seen with Turner (45,XO) and Klinefelter (47,XXY) syndromes. (Choice A) During DNA replication, positive supercoiling occurs in the region ahead of the replication fork and must be removed for DNA replication to proceed. Topoisomerases reduce DNA supercoiling by nicking the DNA strands, introducing negative coiling, and religating the strands. (Choice B) Double-strand DNA breakage can occur following exposure to ionizing radiation. Compared to single-strand breakage, double-stranded breaks are more prone to result in faulty repair, leading to mutations, malignancy, or cell death. (Choice D) Repair of mismatched bases occurs throughout the genome during DNA replication. Impaired mismatch repair is associated with hereditary nonpolyposis colorectal cancer. Educational objective: X-inactivation occurs in genetically normal females and results in conversion of the inactivated X chromosome into compact heterochromatin (Barr body). Heterochromatin is condensed chromatin composed of heavily methylated DNA in tight association with deacetylated histones. It has a low level of transcriptional activity. In contrast, euchromatin is loosely arranged and exhibits a high level of transcriptional activity.

A 24-Year-Old Woman Comes to the Office After Discovering a New